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15 January 2021
Amid skyrocketing cases, Biden unveils $20 billion national vaccination plan to speed vaccine rollout and get more shots into arms
WILMINGTON, Del., January 15 – Five days ahead of his inauguration, President-elect Joe Biden outlined his five-point national vaccination plan to ramp up vaccine rollout and speed up vaccinations as one of his first priorities when he takes office on January 20. The plan comes 24 hours after Biden proposed a $1.9 trillion relief package to combat the economic downturn and the Covid-19 crisis.
The $1.9 trillion package includes more than $400 billion to combat the pandemic directly – of which $20 billion is to accelerate vaccine deployment – signaling Biden’s promised shift in the federal government’s pandemic response. The $20 billion comes on top of some $8 billion already approved by Congress.
Biden’s “rescue” proposal, which would be financed entirely through increased federal borrowing, flows from the idea that the virus and the recovery are intertwined and that the economy cannot rebound without mass vaccine deployment.
The President-elect has said repeatedly that he intends to get “100 million Covid vaccine shots into the arms of the American people” by his 100th day in office, April 30.
On day one, Biden said he plans to instruct the Federal Emergency Management Agency (FEMA) to start opening the first of thousands of federally supported community vaccination centers across the nation, with support from the National Guard. By the end of his first month in office, 100 of these centers will be open, Biden said, at places that are convenient and accessible, such as school gymnasiums, community centers and sports stadiums.
“As we build them, we're going to make sure it's done equitably,” Biden said. “We're going to make sure there are vaccination sites in areas hit harder by the pandemic, in Black and Hispanic communities as well.”
Within the first month, his administration also plans to promote mobile vaccination clinics “to hard-hit and hard-to-reach communities in cities, small towns and in rural communities,” he said.
“One thing that’s clear is that the issue of getting 100 million doses in the first 100 days is absolutely a doable thing. The feasibility of his goal is absolutely clear. There’s no doubt about that, that that can be done. We are weeks away, not months away from considering the approval of new coronavirus vaccines.”
Anthony Fauci, MD
Chief Medical Adviser on COVID-19 to the President
Director, National Institute of Allergy and Infectious Diseases
Speaking on NBC’s “Meet the Press” on January 17, Fauci said two new vaccines under development by AstraZeneca and Johnson & Johnson could “very soon” be presented to U.S. regulators for approval, which would increase the pace of vaccinations. “We’re weeks away, not months away, for sure,” he said.
“We don’t have enough vaccine. We're not going to be able to do this just with mRNA vaccines. We are going to have to accelerate the timetable for the other types of vaccines. We need the two adenovirus vaccines from J&J and AstraZeneca/Oxford, the particle vaccine from Novavax. We have got to get those up to get the vaccines.”
Peter Hotez, MD, PhD
Professor of Pediatrics and Molecular Virology
Baylor College of Medicine
Thirdly, the administration plans to “fully activate the pharmacies across the country to get the vaccination into more arms as quickly as possible,” Biden said. This will include working with both independent and chain pharmacies to help people more easily make appointments.
Biden’s plan would fund the hiring of 100,000 public health workers, to focus on encouraging people to get vaccinated and on tracing the contacts of those infected with the virus.
The fourth point of the plan involves ramping up vaccine supply through the Defense Production Act, Biden said.
“We'll use the Defense Protection Act to work with private industry to accelerate the making of materials needed to supply and administer the vaccine, from tubes and syringes to protective equipment,” Biden said.
Lastly, Biden promised transparency on vaccine supply. “We're going to make sure state and local officials know how much supply they'll be getting and when they can expect to get it so they can plan,” he said. “Right now, we're hearing that they can't plan, because they don't know how much supply of vaccines they can expect at what time frame.”
Biden stressed that his administration is not changing the FDA's recommended dosing schedules. “We believe it's critical that everyone should get two doses within the FDA-recommended time frame. So we're not doing away with that availability,” he said.
The Trump administration has been criticized for its response to the pandemic and has faced questions about the speed and effectiveness of its vaccine rollout. It fell considerably short of its goal to immunize 20 million people by the end of 2020.
Some of Biden’s top Covid response advisers predict a slow start to the ‘100 million vaccines in 100 days’ goal due to the situation they are inheriting and funding shortfalls, and are already warning that the early days of that effort are going to be rocky.
“The first days of that 100 days may be substantially slower than it will be towards the end,” said Michael Osterholm, a member of Biden’s Covid-19 task force who called the goal “aspirational … but doable. It’s not going to occur quickly … you’re going to see the ramp-up occurring only when the resources really begin to flow.”
House Speaker Nancy Pelosi and Senate Minority Leader Chuck Schumer welcomed “the robust package” proposed by Biden as the right approach, saying in a statement, “We will get right to work to turn President-elect Biden's vision into legislation that will pass both chambers and be signed into law.”
Updated on January 18 to feature quote from Dr. Fauci
10 January 2021
Expanding access to vaccines in Brazil: Scientists weigh in on the challenges and opportunities that lie ahead
RIO DE JANEIRO, January 10 – Three of the world’s top vaccine experts, Jeremy Farrar, Peter Piot, and Seth Berkley, open up in response to questions about access to COVID-19 vaccines posed by Mauro Schechter in an article in O Globo, one of Brazil’s most influential newspapers.
There was a powerful common thread to the story – the need for action now that life-saving vaccines are becoming available, the need for resources to support the rollout, overcoming vaccine hesitancy, combined with an optimism that the challenges can be met.
The topics discussed ranged from ways to deal with anti-vaccination movements, “negationist” governments and denialism, the prevention of asymptomatic infection and severe disease, vaccine safety and allergic reactions, the option of postponing the second dose in order to rapidly vaccinate more people, mixing vaccines, the duration of vaccine-induced immunity, the impact of new coronavirus variants on vaccine efficacy, and when the COVAX Facility will have enough vaccines to distribute to all participating countries.
Here are some highlights:
From a public health perspective, how important are the reported efficacy differences in preventing symptomatic disease between the various vaccines?
“All of the vaccines now being deployed and those in late-stage development have efficacy against symptomatic disease that is beyond what many of us dared dream of a year ago when we started on this path. There clearly is immunity to this virus and the vaccines have been able to provide incredible efficacy. But vaccine efficacy is only one element. What matters is not a vaccine, or a vaccine efficacy, what matters is making vaccines available to everyone, to offer and deliver vaccinations, equitably and universally, independent of the ability to pay. This is a scientific imperative. None of us are safe until we are all safe. It is also a moral imperative. Investment in vaccines, diagnostics and treatments are the only way out of this awful pandemic. It would be the greatest investment humanity ever made” – Dr. Jeremy Farrar, Director, Wellcome Trust
It seems that, as it was the case with other vaccines, developing countries are being left behind. The goal of COVAX is to help provide access to COVID-19 vaccines to the most vulnerable in all participating economies. How close are you to this goal? What are the main hurdles? How do you evaluate Brazil's participation and how could both the country and Brazilian society help COVAX?
“It was less than three months ago that COVAX declared itself open for business, with the commitment of 64 self-financing participants. Thanks to unprecedented international collaboration and vaccine manufacturers that share its ambition for global, equitable access, COVAX is now ready to start delivering doses in the first quarter of 2021, with 190 economies now committed. Through agreements with manufacturers, Gavi on behalf of COVAX has secured 1.97 billion doses. Additionally, CEPI has secured a potential further 1 billion doses in 2021 through R&D partnership agreements. We are moving swiftly on funding, while seeking to raise an additional $2.8 billion in 2021 ($800 million for research and development, at least $1 billion for the COVAX AMC and $1 billion for delivery support). To meet our goal of ending the acute phase of the pandemic by delivering 2 billion doses globally in 2021 we still face a number of challenges: not just securing more doses and more funding, but managing other complexities, such as regulatory approvals, readiness and capacity, cold chain, supply chain, delivery and logistics. Now that we are preparing to deliver doses, these are all now urgent challenges. COVAX’s success will depend on its ability to harness the power of international cooperation and public-private partnership. As the most populous nation in Latin America and one that has valued public health interventions, as well as being a key global economy, Brazil has an important role to play and we look forward to working with the government to protect its population and the region more broadly.” – Seth Berkley, CEO, Gavi Alliance
“The U.S. Food and Drug Administration had said it would consider granting emergency approval for vaccines that showed just 50% efficacy. Of the six vaccines (Pfizer/BioNTech, Moderna, AstraZeneca/Oxford, Sputnik, Sinovac, and Sinopharm) that have received either emergency use authorization or full approval in different countries, they have all reached at least 60% or above vaccine efficacy that is way above the U.S. FDA requirement of 50% efficacy. Having said this, the two mRNA vaccines seem to offer the best protection at the moment. However, a safe and effective vaccine itself does not save lives but vaccination of such vaccines does. It is now critical to get these vaccines to as many people in at-risk groups in the world as quickly as possible in order to change the course of the pandemic. Ultimately, it will be issues such as longevity of protection, adverse effects, single or double injection, logistic issues, price, and manufacturing capacity, which will determine which vaccine to use by a country.” – Professor Peter Piot, Special advisor to European Commission President on COVID-19 response
These are just some of the responses selected by O Globo in anticipation that vaccines will soon become available in Brazil. As evidence of momentum, ANVISA on Friday granted an emergency use authorization for the Oxford/AstraZeneca vaccine, and is reviewing a request submitted by Instituto Butantan for the Sinovac vaccine that it tested in its Phase 3 trial. Both vaccines will be manufactured in Brazil by Fiocruz and Butantan, respectively. Between them, the two giant vaccine makers can produce over 50 million doses per month.
8 January 2021
Sinovac’s vaccine is 78% effective in Brazil late-stage trials, but details are sparse
SÃO PAULO, Brazil - State officials yesterday said that an inactivated vaccine developed by Beijing-based Sinovac Biotech, called CoronaVac, was safe and 78% effective in preventing symptomatic COVID-19 disease, and 100% effective in preventing severe disease. The announcement came just as the country marked a grim milestone surpassing 200,000 deaths from the virus, second only to the U.S
Instituto Butantan, the São Paulo-based research center testing CoronaVac in a randomized, placebo-controlled Phase 3 trial launched in July, said that none of the volunteers who were given the vaccine developed severe cases of disease. More than 12,000 health workers took part in the trial, the largest conducted to date in Brazil, the first country to complete tests of Sinovac’s vaccine.
The Sinovac vaccine has shown similar levels of protection (75-85%) in the United Arab Emirates.
Butantan said that full CoronaVac data would be published in a scientific journal soon but did not elaborate. When pressed by reporters, the institute said there had been 218 COVID-19 cases in the trial, 160 of which occurred among participants who received a placebo, compared to 58 among vaccinated volunteers.
Of note, unlike some vaccine trials, the Butantan study included elderly volunteers, a particularly vulnerable population. Unlike mRNA vaccines, Coronavac can be shipped and stored at normal refrigerator temperatures, raising hopes it can be widely deployed in Brazil and the developing world.
Officials were hopeful that Brazil’s national health regulatory agency, ANVISA, would approve emergency use of the vaccine within days. If granted, Brazil could produce up to one million doses of the vaccine per day.
Encouragingly, 80% of Brazilians said they would get a COVID-19 vaccine if one were available, according to a survey last month.
“The results from this Phase 3 trial are pretty impressive. To my mind, all COVID-19 vaccines so far, from a public health perspective, far exceed expectations and are ready for prime time. I think we need to vaccinate as many people as we can, as far and as fast as we can.”
Mauro Schechter, MD, PhD
Professor of infectious diseases
Universidade Federal do Rio de Janeiro
Rio de Janeiro, Brazil
30 December 2020
UK regulator approves Oxford-AstraZeneca vaccine
LONDON, December 30 – In another first, UK regulator MHRA today approved the Oxford-AstraZeneca COVID-19 vaccine for use in Britain. The nod comes amid rising concerns about a new fast-spreading variant that is estimated to be 50% to 70% more transmissible.
The Oxford vaccine is the first adenovirus-vectored vaccine for COVID-19 to be approved in the West. The authorization is for two full doses of the vaccine to be given, with a gap of between four and 12 weeks between them.
Data published in The Lancet on December 8 show the vaccine was 62% effective in preventing COVID-19 in a group of 4,440 people given two standard doses, yet offered 90% protection in a subgroup of 1,367 people who were given a first half dose followed by a full second dose.
The Lancet data set out the full results from clinical trials involving more than 20,000 people. Safety and efficacy were based on an interim analysis of pooled data from four randomized controlled trials conducted in the UK, Brazil, and South Africa.
The vaccine’s ultimate effectiveness and the ideal dosing interval remain to be determined in ongoing and follow-up studies.
Hailed as a game changer by health officials, the Oxford vaccine boasts several advantages. First, unlike mRNA vaccines it doesn’t need to be stored at ultra-cold temperatures. Second, the jab is better tolerated when administered. Third, it is significantly cheaper and is being offered by AstraZeneca at cost, between $3 to $4 per dose.
Indian regulators are expected to follow the UK’s lead and approve the Oxford vaccine within the next 24 hours.
“AstraZeneca will soon release data showing that the effectiveness of its COVID-19 vaccine rises to as much as 95% if you just keep a two-to-three months’ gap between dose 1 and dose 2."
Chief Executive of Serum Institute of India
AstraZeneca’s manufacturing partner
Speaking at a press conference in Delhi and Pune on December 28
17 December 2020
FDA panel recommends emergency use authorization for Moderna COVID-19 vaccine
WASHINGTON, DC. The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) today recommended that the FDA grant an Emergency Use Authorizwation (EUA) for the Moderna vaccine for the prevention of COVID-19 disease in individuals 18 years of age and older.
The recommendation comes hard on the heels of its advice last week that the FDA issue an EUA for the Pfizer/BioNTech COVID-19 vaccine for individuals 16 years and older, and the FDA granting the EUA 24 hours later.
On this occasion, the vote was 20-0 in favor with one abstention.
Updated data from Moderna’s randomized, placebo controlled Phase 3 trial enrolling over 33,000 participants demonstrated the vaccine was 94.1% effective at preventing COVID-19 disease (p<0.0001), with no serious safety concerns.
Among people under 65 years of age, the vaccine was 95.6% effective in preventing disease, and 86.4% in adults 65 and older. The high rate of protection was maintained across genders, racial and ethnic groups and people with medical conditions associated with high risk of severe disease.
The vaccine also showed evidence of preventing severe COVID-19, in addition to asymptomatic infection.
Moderna’s mRNA vaccine is similar in nearly all respects to Pfizer’s. The spike (S) protein used as antigen is essentially the same, and both are formulated in lipid nanoparticles. Both vaccines are administered in two doses. One difference is the dose, 100mg vs. 30 mg, and Moderna’s is administered 28 days apart instead of Pfizer’s 21 days.
There are differences in the exact formulation of the two vaccines, especially with regard to the lipid nanoparticles component. A major benefit is that the Moderna vaccine can be shipped and stored at regular freezer temperatures.
Ongoing and future studies will focus on determining the vaccine’s duration of protection, whether it protects against transmission, and eliciting the correlates of protection from immunological studies comparing T and B cell responses from protected individuals with breakthrough cases. There will also be studies to further look at safety.
As they did last week, it is expected that the FDA will follow its advisory panel’s advice and formally issue the EUA within the next 24 hours, meaning that shipments of the Moderna vaccine could start shortly thereafter.
“Results from the Pfizer/BioNTech and Moderna Phase 3 trials provide resounding validation of the safety and efficacy of the mRNA/lipid nanoparticle platform in delivering such a high level of protection against COVID-19 disease. As such, the platform holds great promise for the design of future vaccines."
Foundation for Vaccine Research
10 December 2020
FDA panel recommends emergency use authorization for Pfizer/BioNTech COVID-19 vaccine
WASHINGTON, DC – In another first in the battle against the pandemic, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) today recommended granting an Emergency Use Authorization (EUA) for the Pfizer/BioNTech vaccine for the prevention of COVID-19 disease in individuals 16 years of age and older. The vote was 17-4 in favor, with one abstention.
The vaccine is an mRNA-based construct encoding for a prefusion stabilized form of the SARS-CoV-2 spike (S) protein formulated in lipid nanoparticles. The S protein complex binds to the human ACE2 receptor necessary for membrane fusion and host cell infection. Like many other COVID-19 vaccines, the vaccine requires two doses, in this case 21 days apart.
The nod followed a virtual meeting of VRBPAC which met in open session to review the data from a randomized, placebo-controlled Phase 1/2/3 pivotal registration study conducted by Pfizer and BioNTech. The initial trial design began as a Phase 1/2 study in the U.S. The study was revised to an adaptive clinical trial design, with agreement from the FDA, and subsequently expanded to a global Phase 3 study enrolling ~44,000 participants at selected sites across the globe to ensure population diversity.
Results from the ongoing Phase 3 study showed that the vaccine was well tolerated, safe and 95% effective 7 days after the second dose was given in preventing COVID-19 disease. Encouragingly, the 95% efficacy rate held among people 55 years of age and older.
The panel’s assessment was based on a rolling review of the safety, immunogenicity and efficacy data from the Phase 1, 2 and 3 trials, which demonstrated a vaccine efficacy rate of 95% (p<0.0001) consistent across all age groups, genders, racial and ethnic groups, and people with medical conditions associated with high risk of severe disease.
Safety data from ~38,000 participants ≥16 years of age randomized 1:1 to vaccine or placebo with a median of 2 months of follow-up after the second dose suggest a favorable safety profile, with no specific safety concerns identified that would preclude issuance of an EUA.
Available safety data from all participants enrolled through the November 14 data cut-off (43,252 in total, which includes late enrollment of additional adolescent and adult participants), were consistent with the safety profile for the 38,000 participants with median follow-up of 2 months and also did not raise specific safety concerns.
The FDA rarely goes against its advisory committee and is expected to follow its advice, although FDA is not obligated/required to follow the committee’s recommendations.
The FDA panel’s verdict comes on the heels of the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) granting an emergency use authorization for the Pfizer/BioNTech vaccine on December 2, and Health Canada approving the vaccine yesterday.
These announcements come just 11 months after the genetic sequence of the novel coronavirus, later named SARS-CoV-2, was released by the Chinese on January 12. Never has a vaccine been developed and authorized for use in humans within such a short timeframe.
Adding to the excitement that the end of the pandemic may be in sight, the FDA is expected to grant an EUA for Moderna’s mRNA vaccine against COVID-19, which is not dissimilar to the Pfizer/BioNTech vaccine, following a meeting of the VRBPAC panel on December 17.
“From discovery to regulatory authorization for distribution of a vaccine against a novel virus in less than a year is a significant milestone for science and public health…all involved in this endeavor are to be commended!”
Norman W. Baylor, PhD
President and CEO
Former Director, Office of Vaccines Research and Review/US FDA/CBER
6 March 2020
Trump signs $8.3 billion coronavirus package
WASHINGTON, DC – President Trump on Friday signed the bill providing $8.3 billion in emergency supplemental funding to combat the coronavirus outbreak.
Trump was originally expected to sign the bill at CDC headquarters in Atlanta, Ga., on Friday but abruptly cancelled his trip there, telling reporters Friday morning that the trip was cancelled because of a suspected coronavirus case at the CDC itself but that it turned out to be negative.
The House and Senate passed the funding measure in overwhelming bipartisan votes on Wednesday and Thursday, respectively, sending the bill to the president’s desk.
Trump’s signing of the bill on Friday capped a week of intense negotiations on Capitol Hill to secure a deal on the funding and rapidly pass the legislation in both chambers.
The bill includes $3 billion in new money to speed the research and development of vaccines, therapeutics and diagnostics.
The Foundation for Vaccine Research applauds the Congressional leadership and strong bipartisan support for this supplemental bill and the speed with which it was approved.
While only a portion of the $3 billion will go directly toward advancing research and development of a SARS-CoV-2 vaccine, the boost in funding marks a promising start.
An additional investment will be required as clinical trials start – the first phase 1 study has begun recruiting participants in Seattle – and, looking further ahead, to finance the building of manufacturing capacity that will be required to produce millions of doses of vaccines.
5 March 2020
Senate approves $8.3 billion emergency supplemental funding request for coronavirus response
WASHINGTON, DC – Congress cleared an $8.3 billion emergency supplemental funding package intended to bolster public health resources and assuage fears as the novel coronavirus continues to spread throughout the country.
The Senate voted 96-1 following limited debate on the legislation, sending it to President Donald Trump who is expected to sign it quickly. The 28-page bill was released Wednesday afternoon, following days of intense behind-the-scenes debate on its size and scope. The House passed the bill by a 415-2 vote just hours after it was introduced.
The $8.3 billion package includes $3 billion in new money for NIAID and BARDA, to advance the research and development of vaccines, therapeutics and diagnostics. Of this, NIAID will receive $836 million, while BARDA will receive $2 billion.
Missing from the package is any provision to surge manufacturing capacity which the Foundation for Vaccine Research has identified as a key rate-limiting factor in the deployment of a safe and effective vaccine to curb the virus’s spread.
This article will be updated
24 February 2020
Moderna ships first batch of its candidate mRNA vaccine against SARS-CoV-2 for phase 1 study
CAMBRIDGE, Mass., February 24: Moderna today announced that it has dispatched the first clinical batch of mRNA-1273, the company’s vaccine against the novel coronavirus SARS-CoV-2, for human use. Vials of mRNA-1273 have been shipped to NIAID to be used in a planned phase 1 study to be conducted by the Institute.
Moderna thus becomes the first of two dozen biotechs and larger companies working on developing a SARS-CoV2 vaccine to push a preventative vaccine for the outbreak to trial.
NIAID has said that it expects by the end of April to start a clinical trial of about 20 to 25 healthy volunteers, according to sources. The study will test whether two shots of the vaccine are safe and induce an immune response likely to protect against infection. Initial results of the study could become available in July or August.
mRNA-1273 is an mRNA-based vaccine encoding for a prefusion stabilized form of the spike (S) glycoprotein. The S protein complex binds to the human ACE2 receptor necessary for membrane fusion and host cell infection and has been the target of vaccines against the coronaviruses responsible for MERS and SARS.
The SARS-CoV-2 vaccine chosen for the first human study was one of a pool of five candidates that encode a version of the viral spike protein designed by a team at NIAID’s Vaccine Research Center in collaboration with Moderna in Cambridge.
The conformation of the spike protein changes shape as it interacts with the human ACE2 receptor. As a result the areas of the protein most important for that interaction can become hidden from the immune system. Mutations were made to the spike-encoding gene so that the protein it encodes stays in a stable, “prefusion” form.
In animal studies, the stabilized form of the MERS spike protein was shown to elicit a stronger immune reaction than the native form. Initial data on the mouse immune responses to SARS-CoV-2 stabilized spike protein are expected around the end of March, according to Moderna.
If the phase 1 trial starts as planned in April, it would be about three months from vaccine design to human testing. In comparison, after an outbreak of SARS in China in 2002, it took about 20 months for NIAID to get a vaccine into the first stage of human testing. Moderna’s turnaround time in producing the first batch of vaccine represents a stunningly fast response to an emerging outbreak.
“Going into a phase 1 trial within three months of getting the sequence is unquestionably the world indoor record,” said NIAID Director, Dr. Anthony Fauci. “Nothing has ever gone that fast.”
19 February 2020
UT scientists produce first 3-D map of new coronavirus
In a breakthrough achievement that could speed the development of a SARS-CoV-2 vaccine, a team of scientists at the University of Texas at Austin led by Dr. Jason McLellan, working with researchers at the NIH, has produced the first 3-D map of the coronavirus spike glycoprotein.
The research, which maps the molecular structure of the SARS-CoV-2 spike, was published in the journal Science on Wednesday.
The team successfully produced a 3-D atomic-level scale map of the part of the virus that attaches to and infects human cells. That part – called the spike (S) glycoprotein – could prove essential as researchers race to produce a vaccine.
The Austin team had already been studying other viruses in the coronavirus family and developing ways of locking their spike proteins into a shape that made them easier to analyze.
This enabled them to design and produce samples of their spike protein within two weeks of receiving the genetic sequence of the virus from Chinese researchers. It then took just another two weeks to reconstruct the 3-D atomic-scale map.
Since the SARS-CoV-2 spike (S) glycoprotein is a key target for vaccine and antiviral drug design, the team determined a 3.5 Å-resolution cryo-EM structure of the spike trimer in the prefusion conformation (see schematic).
Among their discoveries, they found that the predominant state of the trimer has one of the three receptor-binding domains rotated up in a receptor-accessible conformation.
Of interest to scientists trying to make sense of the rapid spread of the new coronavirus, the team also showed biophysical and structural evidence that the spike protein of SARS-CoV-2 binds the human receptor ACE2 with ~10- to 20-fold higher affinity than ACE2 binding to SARS-CoV.
This finding led the team to conclude that the higher affinity of the SARS-CoV-2 spike protein for human ACE2 receptor may contribute to the apparent ease with which the new coronavirus can spread from human-to-human.
Knowing the atomic-level detail of the structure of the spike will support precision vaccine design and additional protein engineering efforts that could improve the antigenicity and protein expression of candidate vaccines, as well as the development of coronavirus spike inhibitors.
18 February 2020
Sanofi joins forces with BARDA to advance a SARS-CoV-2 vaccine
PARIS, February 18: Sanofi Pasteur today announced they will leverage advanced pre-clinical work for a SARS-CoV vaccine conducted several years ago which may unlock a fast path forward for developing a vaccine against the new coronavirus, SARS-CoV-2 (previously known as 2019-nCoV). Sanofi will link up with BARDA, the Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services in Washington, DC, expanding the company’s long-standing partnership with BARDA.
Sanofi will use its well-established, licensed recombinant DNA platform to speed the development of a SARS-CoV-2 vaccine candidate. The novel coronavirus shares ~77% sequence homology with the spike (S) glycoprotein of the SARS-CoV that caused the 2002-2003 SARS outbreak in China that resulted in over 8,000 cases and 774 deaths worldwide. The new coronavirus is more readily transmitted than SARS-CoV, but not as deadly.
Sanofi’s recombinant technology produces an exact genetic match to the proteins on the surface of the coronavirus. The DNA sequence encoding this antigen will be combined into the DNA of the baculovirus expression platform, the basis of Sanofi’s licensed recombinant seasonal flu vaccine, Flublok – the only FDA-approved recombinant protein-based flu vaccine – and used to rapidly produce large quantities of the coronavirus antigen which will be formulated to stimulate the immune system to protect against the virus.
Sanofi’s proprietary platform was developed by Protein Sciences, a Meriden, Connecticut-based biotech which Sanofi acquired in 2017 for $750 million. Sanofi hopes their earlier work on developing a SARS-CoV vaccine will provide a head start in the race to develop a SARS-CoV-2 vaccine. In preclinical studies, their SARS-CoV candidate was shown to be immunogenic and afforded partial protection in animal challenge models.
The existence of a licensed vaccine based on this platform will allow for research and materials to be produced relatively quickly for clinical testing, according to Sanofi. The platform also has the potential to manufacture large quantities of the vaccine candidate.
In December 2019, Sanofi also cemented an agreement with BARDA to establish state-of-the-art facilities in Swiftwater, PA for the sustainable production of an adjuvanted recombinant vaccine for use in the event of an influenza pandemic based on the same technology platform that will be used for their SARS-CoV-2 program.
The contract will support the clinical development and manufacturing of an adjuvanted recombinant pandemic vaccine and expand Swiftwater's role as a center of excellence for pandemic preparedness by adding both recombinant and adjuvant manufacturing alongside current egg-based manufacturing.
30 January 2020
WHO declares global public health emergency
GENEVA, January 30: After a week of growing alarm which saw the number of confirmed cases of people infected with the novel coronavirus soar to more than 7,800, close to the number of infections with SARS during the 2002-2003 epidemic, the WHO today took decisive action and formally declared that the Wuhan outbreak constitutes a public health emergency of international concern.
A key factor in reaching their decision – which the WHO had initially been reluctant to make – was that the outbreak was no longer limited to China but had spread rapidly to 18 other countries. Among them, Australia, Vietnam and South Korea which all announced new infections today, while India and the Philippines reported their first cases, and the CDC announced the first person-to-person transmission of the virus in the U.S.
The global health agency met twice last week in Geneva but was split about whether to declare an emergency, saying it did not have enough information to decide. Such rulings can rally a global response, but also put countries at the center of any outbreak under even greater scrutiny, which many WHO member states are eager to avoid because of socioeconomic and other impacts.
"The main reason for this declaration is not because of what is happening in China but because of what is happening in other countries," said WHO chief Tedros Adhanom Ghebreyesus. “Our greatest concern is the potential for the virus to spread to countries with weaker health systems, and which are ill-prepared to deal with it.”
The declaration gives WHO certain capabilities to help facilitate containment of the virus globally and would also allow WHO to put travel advisories in place. Although WHO recommendations are not enforceable, member states usually follow them. The declaration has the effect of galvanizing governments to take action.
Also on Thursday, the WHO said it plans on provisionally calling the disease caused by the virus “2019-nCoV acute respiratory disease” until officials settle on a name.
29 January 2020
Australian researchers first to grow Wuhan coronavirus in cell culture
MELBOURNE, January 29: Researchers in Melbourne are the first group outside China to announce that they’ve grown the new Wuhan coronavirus 2019-nCoV in cell culture. This marks a significant advance in the race to develop a vaccine.
The team at Peter Doherty Institute for Infection and Immunity says it isolated the virus from the first person diagnosed with the infection in Australia, on January 25.
The team will now share the virus with research labs around the world to help speed the development of more accurate diagnostic tests and the development of a vaccine, says Mike Catton, deputy director of the institute.
Scientists in China have also been able to grow the virus in the lab but have not yet shared samples with international researchers – they have shared only the virus’s genetic sequence.
Having live virus samples will enable scientists to create tests that can detect antibodies that indicate whether a person has been infected with the new virus. Equally important, having live virus samples can help advance vaccine design.
Ian Mackay, a virologist at the University of Queensland, Brisbane, heralded the Melbourne group’s announcement as “fantastic news.” He says lab-grown samples are essential for research into the behavior of the virus in culture or in animal hosts.
23 January 2020
Moderna, Novavax and other biotechs join race to develop a Wuhan coronavirus vaccine
Less than 10 days after the genetic sequence of the SARS-like Wuhan coronavirus, 2019-nCoV, was released from China and published in GenBank on January 12 (updated January 17), at least four U.S. biotech companies and 2 other groups have jumped into the race to develop a vaccine against the deadly disease.
Analysis of the sequence data shows the novel coronavirus shares ~75% spike glycoprotein identity/homology to the SARS virus which, according to experts, suggests the design of a vaccine using published prefusion-stabilizing mutations may be a promising avenue to readily discover and develop a vaccine.
While the characteristics of the Wuhan glycoprotein spike have not yet been fully defined as compared to other coronaviruses, scientists are hopeful that they will be able to rapidly identify key vaccine targets and with novel vaccine platforms “ready to go” could develop a candidate vaccine for testing in six weeks.
Experts caution that developing a vaccine will, however, take at least a year and likely close to two years for a vaccine to be available on an emergency-use basis.
Moderna is partnering with NIH/NIAID/VRC on developing a mRNA vaccine against 2019-nCoV, taking the gene for the spike protein S and inserting it into one of their rapid and flexible mRNA-based vaccine platforms to create a vaccine.
Unless there are unforeseen obstacles, NIAID says they could likely start a Phase 1 trial in about 90 days. VRC has sufficient funds to cover the cost of developing a candidate vaccine and conducting a Phase 1 trial, according to NIAID.
It should be noted that Moderna’s rapid response capability has not been previously tested.
Novavax has started development of a vaccine to protect against 2019-nCoV, the company has confirmed. Their candidate will be based on Novavax’s recombinant nanoparticle vaccine technology and would incorporate their proprietary saponin-based Matrix-M adjuvant. Like Moderna, Novavax has also said they could have a candidate vaccine ready for Phase 1 trials in 90 days.
Two other biotechs are also entering the fray, according to sources. Inovio is working on developing a DNA vaccine against the SARS-like virus based on their previous work developing vaccines against SARS and MERS-CoV.
In addition, Codagenics is considering applying their revolutionary technology to developing a novel vaccine approach against 2019-nCoV based on live-attenuated virus design. The Codagenix platform is based on a computer algorithm that rationally “redesigns” viral genomes to reduce viral gene function. These artificially designed viruses function as live-attenuated vaccines that stimulate T cell and antibody responses but are non-pathogenic.
In Houston, scientists at the National School of Tropical Medicine at Baylor Medical School are working on a more classical approach. The Baylor team has received NIH funding since 2012 to collaborate with the New York Blood Center and the University of Texas Medical Branch at Galveston on a SARS vaccine.
Baylor’s SARS vaccine is based on recombinant receptor-binding domain of the SARS-CoV spike (S) protein. Because there are similarities between the new coronavirus and SARS, Baylor hopes their vaccine may be able to cross-protect against the new virus, though it is unknown whether the difference in viral spike genes is too great to enable cross-protection. If their vaccine is shown to be cross-protective in animal studies, Baylor and its partners could start Phase 1 trials quickly.
The Canadians have also jumped into the race building on their experience with SARS. The University of Saskatchewan's Vaccine and Infectious Disease Organization - International Vaccine Centre (VIDO-InterVac) has also started developing a vaccine, using their expertise developing next-generation viral vectors.
While these noteworthy efforts are under way, the Chinese and other groups around the world will doubtlessly be ramping up their own programs in the race to develop a safe and effective vaccine against this new threat. Based on their prowess developing vaccines against pandemic influenza and other exotic pathogens, Chinese vaccinologists may already be ahead of the game and the ones to watch.
This story will be updated
03 January 2020
BCG vaccine provides almost complete protection against tuberculosis in macaques when injected intravenously
A team of NIH scientists and their colleagues from the University of Pittsburgh has shown that simply changing the dose and route of administration of the BCG vaccine from intradermal (ID) to intravenous (IV) dramatically increases the vaccine’s ability to protect rhesus macaques from infection following exposure to Mycobacterium tuberculosis (Mtb), the bacterium that causes TB. This is a striking improvement over vaccination through the typical intradermal route.
The findings published this week in Nature come just two months after a multinational team reported in The New England Journal of Medicine the final results of a large multi-center Phase 2b study showing that GSK’s candidate TB vaccine, M72/AS01ᴇ, provides 50% protection against pulmonary TB in adults with latent TB infection during the three years after vaccination (see our October 29 story, First real hope for an improved TB vaccine in 100 years).
The NIH study results are compelling and may provide a new understanding of the mechanisms of BCG-elicited protection against TB infection and disease, say experts. In addition, the findings would seem to support investigation of IV administration of the BCG vaccine in human clinical trials to determine whether this route improves its effectiveness in adolescents and adults.
To control TB infection and prevent clinical disease, conventional wisdom holds that a TB vaccine must elicit strong, sustained responses from the immune system’s T cells, specifically those in the lungs. However, the standard intradermal route of BCG administration may not generate enough of these critical cells in the lungs.
NIH scientists hypothesized that administration of the BCG vaccine by intravenous (IV) or aerosol (AE) routes instead of intradermal (ID) could overcome this hurdle and thus confer substantially better protection from infection and/or disease in rhesus macaques following challenge with a virulent strain of Mycobacterium tuberculosis to which the animals are particularly susceptible.
In the NIH study, groups of animals received the BGC vaccine by ID, AE or IV routes. Scientists assessed immune responses in blood and in fluid drawn from the lungs for a 24-week period following vaccination and compared these responses to each route as well as to unvaccinated animals. Findings showed that IV BCG vaccination resulted in the highest durable levels of T cells in the blood and lungs.
Six months after vaccination, researchers exposed groups of vaccinated macaques (immunized via ID, AE or IV routes) and unvaccinated macaques to a virulent strain of Mtb by introducing the bacteria directly into the animals’ lungs. They then tracked the infection and disease development in each animal over three months.
Results: Nine out of 10 animals vaccinated with IV BCG were highly protected; six showed no detectable infection in any tissue tested, and three had only very low counts of Mtb bacteria in lung tissue. All unvaccinated animals and those immunized via ID or AE routes showed signs of significantly greater infection.
Investigators concluded that IV BCG conferred “an unprecedented degree of protection in an animal model of severe TB and represents a major step forward in the field of TB vaccine research.”
The NIH team was led by Robert Seder, MD, and Mario Roederer, PhD, at NIAID’s Vaccine Research Center on the NIH campus in Bethesda. Their collaborators included JoAnne Flynn, PhD, of University of Pittsburgh School of Medicine.
“If we had a highly effective vaccine and it costs 10 cents, but has to be given intravenously, then training people to deliver it would be very reasonable. I have full confidence in my colleagues that if this works well and it’s safe, they will be able to do it.”
Robert A Seder, MD
Chief, Cellular Immunology Section
Vaccine Research Center
National Institute of Allergies and Infectious Diseases (NIAID)
National Institutes of Health
Seder's team is currently conducting studies to test whether lower doses of the BCG vaccine given via IV can still provide protection. In these ongoing studies, high-level protection is reportedly being seen at much lower doses of BCG. Data will be presented at a Keystone conference in Santa Fe, New Mexico, on January 17.
The team is also testing whether T cells are required for the vaccine to provide protection. In this study, scientists plan to deplete monkeys’ T cells after immunization and prior to infection to clarify their critical role in mediating protection.
TB experts not involved in the research are impressed by the study results reported in Nature but sounded a note of caution about proceeding too fast. “We have to start with very careful analysis in the animals before we start any Phase 1 studies,” said Seder. “In both animal studies and clinical trials, we will be very careful and slow and methodical to make sure that the vaccine is safe.”
Any Phase 1 trials will have to answer the all-important question: Is it safe to inject the bacteria in the BCG vaccine straight into a person’s bloodstream?
The BCG vaccine contains live bacteria that has been attenuated (weakened) in a way that makes it possible to create immunity without leading to illness. There are concerns about inundating the circulatory system with live bacteria because it can replicate and potentially cause problems. That is less of a concern when the vaccine is injected under the skin.
If follow-up studies currently under way or planned show that IV BCG vaccination is both safe and more effective, it could still prove a challenge to carry out widespread IV vaccinations, particularly in resource-limited areas where TB is more common. For a vaccine to be delivered intravenously, staff would need specialized medical training and the vaccine would need to be kept cold.
Experts acknowledge these challenges but consider IV BCG vaccinations could one day become feasible. If successful, this would represent a paradigm shift in the way that people are vaccinated against TB infection.
The BCG IV study represents another encouraging step forward in the development of vaccines focused on blocking TB infection by preventing latency, active disease and/or transmission. If safety and efficacy results can be replicated, scientists hope the data will support the clinical development of IV delivery of BCG for use in adolescents or adults in whom modelling predicts the greatest effect on TB transmission.
The studies could also provide a benchmark against which future vaccines can be tested and a new framework to understand the immune correlates and mechanisms of protection against TB.
19 December 2019
In rapid succession, European and U.S. regulators approve first Ebola vaccine
Within the space of five weeks, the European Commission, following a recommendation from the European Medicines Agency (EMA), and the U.S. Food and Drug Administration (FDA) have approved Merck’s Ebola vaccine, Erbevo, as the first ever European- and FDA-approved vaccine for the prevention of disease caused by Zaire ebolavirus in individuals 18 years of age and older.
The duration of protection conferred by Ervebo, known as v920 in its investigational phase, is unknown. In field tests, the vaccine has been shown to be 97.5% protective against Zaire ebolavirus, the species causing the current outbreak in Democratic Republic of Congo (DRC) in which over 2,100 people have already died, and the 2014 West African outbreak. However, it does not protect against other species of Ebolavirus, such as Sudan ebolavirus.
Since August 2018 when the DRC outbreak began, Merck’s experimental vaccine v920 (rVSV-ZEBOV-GP) has been administered to more than 225,000 people and has been found to be safe and effective. Merck has shipped more than 245,000 1.0 mL doses of the vaccine to the DRC.
Merck has said it expects to make licensed doses of its Ebola vaccine available in the third quarter of 2020. In a welcome development, the company has committed to making the single-dose injection available to Gavi-eligible countries at the lowest possible access price but has not yet established the price for the vaccine.
A stockpile of 500,000 doses is being established for emergency use in future Ebola outbreaks. Merck is partnering with both Gavi and the World Health Organization to put that stockpile in place as quickly as possible. The stockpile will be governed and executed by the owner and not by Merck.
The approvals follow the recent announcement of a Phase 1 clinical trial for a second Ebola vaccine regimen, Janssen’s Ad26.ZEBOV, MVA-BN-Filo, that is now under way in the DRC. This stepped-up research activity bodes well for the future, notwithstanding the enormity of the special challenges fighting the DRC outbreak.
The Foundation for Vaccine Research is proud to have played a small part in developing Congressional support for increased U.S. investments in Ebola vaccine research. In September 2014, the Foundation hosted and organized the first U.S. Senate briefing on progress being made in the development of an Ebola vaccine.
6 December 2019
New typhoid fever vaccine shown to protect young children for the first time
A tetanus-toxoid conjugated typhoid vaccine has been shown to reduce cases of the bacterial disease by more than 80% in a Phase 3 trial involving 20,000 children in Nepal. Final analysis of the trial results published in The New England Journal of Medicine showed that a single dose of the vaccine was safe, immunogenic and efficacious.
It is the first time that a conjugated typhoid vaccine has been tested among young children in a large efficacy trial in a typhoid endemic region. A typhoid conjugate vaccine (TCV) was recently pre-qualified by the World Health Organization and was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking.
There is a critical unmet need for a new typhoid vaccine because neither of two existing typhoid vaccines are suitable for young children. One comes in a capsule that is too large for younger children to swallow, so it is for children over 6 years only. The other, delivered as an injection, doesn’t work in children under age 2.
The TCV vaccine used in the trial was a tetanus-toxoid conjugated Vi polysaccharide typhoid vaccine developed by Bharat Biotech International of Hyderabad, India. Tetanus toxoid has been used safely as the carrier in many conjugated vaccines, such as the Haemophilus influenzae type b (Hib) vaccine. The Vi polysaccharide component is a well-standardized antigen prepared from the surface polysaccharide of Salmonella Typhi strain Ty2. The control vaccine was a Meningococcal capsular group A conjugate vaccine developed by Serum Institute of India.
The vaccine was given to 10,005 children in Lalitpur, Nepal, where the disease is endemic. Another 10,014 were immunized against meningococcal disease (MenA) to serve as a control group. One dose was given. It took about a month for the vaccine to provide protection. The primary outcome was typhoid fever confirmed by blood culture.
While 38 children in the control group developed typhoid fever, there were only 7 cases among the 10,005 children given the vaccine. The results were statistically highly significant: 81.6% vaccine efficacy; 95% confidence interval, 58.8 to 91.8; P-value <0.001.
The results could mark a turning point in efforts to curb the number of typhoid infections. Further data are required to show vaccine efficacy in the medium term and long term, the indirect effect and herd immunity achieved from large-scale vaccination, and the vaccine’s effectiveness in different age groups and populations.
A follow-up of the Nepal trial is ongoing, and further trials in Malawi and Bangladesh are under way to address some of these questions. The findings from the Nepal study uphold the recent recommendations of the WHO to use TCV in high-burden settings and to immunize children who are 9 months to 15 years of age.
The study was conducted by the Typhoid Vaccine Acceleration Consortium (TyVAC), a partnership between Oxford University, University of Maryland School of Medicine and the international nonprofit organization PATH. The trial was funded by the Bill & Melinda Gates Foundation under a $36.9 million grant to TyVAC to accelerate the introduction of TCVs into Gavi-eligible countries. The vaccine was donated by Bharat, although Bharat was not otherwise involved in the trial.
29 October 2019
First real hope for an improved TB vaccine in 100 years
GSK’s M72/AS01ᴇ candidate vaccine significantly reduced the incidence of pulmonary tuberculosis disease (TB) in HIV-negative adults with latent TB infection. Results of a Phase 2b study demonstrate an overall vaccine efficacy of 50% during the three years after vaccination.
Final analysis of a large multicenter Phase 2b study published in The New England Journal of Medicine confirms the efficacy and safety of GSK’s adjuvanted recombinant protein vaccine in a three-year prevention of disease (POD) clinical trial conducted in Sub-Saharan Africa. Results showed a 50% efficacy of M72/ASO1ᴇ in reducing the incidence of lung TB disease in HIV-negative adults already infected with latent TB at the time of vaccination.
The trial was conducted in TB-endemic regions (South Africa, Kenya and Zambia) and involved 3,573 HIV-negative adults between the ages of 18 and 50 years. Participants who received two doses of either M72/AS01ᴇ or placebo 30 days apart were followed for three years to detect evidence of pulmonary TB disease.
In the final analysis, 13 participants in the vaccine group developed active pulmonary TB compared to 26 participants in the placebo group. Among participants who received the vaccine, an increased M72-specific immune response was sustained through three years.
The trial was a randomized, double-blind, placebo-controlled study comparing M72/AS01ᴇ to a placebo in a 1:1 ratio. The study was conducted at 11 sites in Africa: 9 in South Africa (Khayelitsha, Worcester), one in Kenya, and one in Zambia. The primary objective of the study was to investigate if M72/AS01ᴇ prevents adults with latent Mycobacterium tuberculosis infection from developing pulmonary TB disease.
Final results confirmed the clinically acceptable safety profile of M72/AS01ᴇ reported one year ago. No patterns were evident in the extended follow-up in terms of occurrence or nature of serious adverse events, fatal events or potential immune-mediated diseases over the study period.
Nearly all participants (99%) in the study consented to enter into a biobanking study sponsored by IAVI. Samples collected during this study will allow researchers to further investigate the potential vaccine-induced mechanisms of protection against TB and attempt to identify markers that indicate those who are protected by vaccine.
M72/AS01ᴇ is a subunit vaccine containing the M72 recombinant fusion protein derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A), combined with GSK’s proprietary Adjuvant System AS01, a powerful liposome/TLR₄ agonist adjuvant which is also a component of GSK’s RTS,S malaria vaccine and GSK’s blockbuster shingles vaccine, Shingrix. (Licensed in October 2017, Shingrix is projected to have racked up sales of $2 billion by end 2019.)
The Phase 2b study was sponsored by GSK and conducted in partnership with IAVI. Funders of IAVI for this study were the Bill & Melinda Gates Foundation, the UK’s Department for International Development (DFID), the Directorate General for International Cooperation in the Netherlands, and the Australian Agency for International Development (formerly AusAID, now Australian Aid).
An improved TB vaccine that is 50% effective in reducing the incidence of pulmonary TB represents a giant step forward in the fight against TB and could save millions of lives, hence the desire to advance M72/AS01ᴇ into late-stage development with a sense of collaboration and urgency.
A Phase 3 trial would not come cheap. It would be an enormous undertaking and require the kind of huge step-up in resources possible only when funders, public and private, work together and share the cost. In April 2019, GSK estimated that the cost of moving M72/AS01ᴇ through Phase 3 to licensure could exceed $800 million, and has made it clear they will be looking for partners.
Regarding timing, GSK has said it was unlikely that Phase 3 could start before 2022, and that global vaccine delivery may not be implemented until 2030.
For public health officials in TB-endemic regions with the highest burden of TB disease, this does not come soon enough. To meet this challenge, WHO has organized expert consultations in Geneva to see what potential Phase 2/3 scenarios and regulatory arrangements could be made to dramatically shorten this timeframe.
TB advocates must that hope that funders will rise to the occasion and do everything possible to speed the further development and rapid deployment of M72/AS01ᴇ to realize its promise as potentially the first new TB vaccine in nearly a century.
See WHO Report High-level consultation on accelerating the development of the M72/AS01ᴇ tuberculosis vaccine candidate, 5 April 2019, Geneva, Switzerland.
12 September 2019
Moderna announces positive results from Phase 1 study of its CMV mRNA-based vaccine
CAMBRIDGE, MA, September 12: Moderna today announced positive data from a three-month interim analysis of a Phase 1 study conducted among 169 healthy adults to evaluate the safety and immunogenicity of its candidate Cytomegalovirus (CMV) mRNA-based vaccine, mRNA-1647.
Vaccination of CMV-seronegative participants raised antibody titers to levels similar to those in participants who were CMV-seropositive due to prior natural infection. Vaccination of those who were already CMV-seropositive strongly boosted their titers. The vaccine was generally well-tolerated.
CMV is a common pathogen and a member of the herpesvirus family and a leading infectious cause of birth defects in America and around the world. Congenital CMV infection results when infected mothers transmit the virus to their unborn child. An estimated 25,000 newborns in the U.S. are infected every year and birth defects occur in about 20% of infected babies. Defects include disabilities such as hearing loss, vision impairment, varying degrees of learning disability and decreased muscle strength and coordination.
There is currently no approved vaccine for the prevention of CMV infection. In 1999, the Institute of Medicine (now National Academy of Medicine) designated CMV as a “highest priority” category for vaccine development. In the twenty years since, CMV has defied all attempts to develop an effective vaccine. Although many candidate CMV vaccines are being tested, no vaccine is close to licensure, and none has achieved titers as high as Moderna’s candidate.
The results of Moderna's Phase 1 clinical trial are impressive, according to experts who have seen the data. Study participants who were “seronegative” for CMV, meaning they were not previously infected, showed three-to-five times higher levels of anti-CMV neutralizing antibodies following injections with mRNA-1647 compared to baseline antibody levels seen in “seropositive” participants, or those previously infected with CMV. At the same time, seropositive participants injected with the vaccine showed levels of neutralizing antibodies that rose 10-19 times over baseline antibody levels.
Despite the study’s small size, researchers agree the encouraging increases observed in neutralizing antibody titers among both vaccinated seropositives and seronegatives warrant prioritizing the further development of mRNA-1647 on an accelerated basis since no other CMV candidate vaccine to date has elicited such high titers.
Moderna is advancing mRNA-1647 to a dose-confirmation Phase 2 study “in the near term” to learn more and see if these results can be replicated. The study protocol is currently being reviewed by the FDA. In parallel, Moderna says it has already begun planning for “a pivotal Phase 3 study” to evaluate the efficacy of mRNA-1647 for the prevention of primary CMV infection in a population that includes women of childbearing age. The Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary lipid nanoparticle (LNP) used in the Phase 1 study.
The Phase 1 trial was a randomized, observer-blind, placebo-controlled, dose-ranging study designed to evaluate the safety and immunogenicity of mRNA-1647 in healthy adults. The study investigated a three-dose vaccination schedule (0, 2 and 6 months) of the vaccine at four dose levels (30, 90, 180 and 300 μg) in both CMV-seronegative and seropositive participants. Primary outcome measures include solicited adverse events. Secondary outcome measures include anti-CMV neutralizing antibody titers against epithelial cell infection and fibroblast cell infection.
The study enrolled 169 healthy adult volunteers. Of these, 134 subjects were immunized with the vaccine. Among these, 64 were naïve to CMV (seronegatives) and 70 had previously been infected by CMV (seropositives). Participants were randomized to receive either placebo, or 30, 90, 180 or 300 µg of mRNA-1647 on a dosing schedule of 0, 2 and 6 months. 35 volunteers were not immunized as the highest dose 450 ug mRNA proposed in the study protocol ended up not being used.
This first planned interim analysis of Moderna's Phase 1 study assessed the safety and immunogenicity of the first three dose levels (30, 90, and 180 µg) at three months, one month after the second vaccination and before the third vaccination.
“We are very pleased with these strong interim results and the immunogenicity demonstrated by our CMV vaccine. The Moderna research, development and manufacturing teams have been working to ensure this program can transition in the near term to a dose-confirmation Phase 2 study, while also preparing for a pivotal Phase 3 study with the goal of ensuring commercial readiness. Given the urgent need for CMV prevention around the world, we believe mRNA-1647 has the potential to be a blockbuster commercial opportunity for Moderna.”
Chief Executive Officer
“I am very encouraged by the ability of mRNA-1647 to induce high levels of durable immune responses that can reach or exceed the levels generated by natural CMV infection. We recognize there is an urgent need for a preventative vaccine against congenital CMV and will be advancing mRNA-1647 into a Phase 2 study in the near term to confirm the appropriate dose, while we plan for a pivotal Phase 3 study.”
Tal Zaks, MD PhD
Chief Medical Officer
Neutralizing antibody titers (levels of circulating antibodies that block infection) were assessed in two assays utilizing epithelial cells and fibroblasts, which measure immune responses to the pentamer and gB vaccine antigens, respectively.
In CMV-seronegative participants:
- A dose-related increase in neutralizing antibody titers in both epithelial cell and fibroblast assays.
- In epithelial cells, after the second vaccination, neutralizing antibody titers were 3 to 5 times higher than titers in unvaccinated seropositives at the 90 and 180 µg dose levels.
- In fibroblasts, after the second vaccination, neutralizing antibody titers were equivalent to CMV-seropositive baseline titers at the 90 and 180 µg dose levels.
- For the 12 sentinel participants who received mRNA-1647 under an earlier arm of the protocol (Phase A) and who received three doses (at 0, 2 and 6 months), neutralizing antibody titers were further boosted at 7 months and were sustained at or above CMV-seropositive baseline levels for at least 12 months.
In CMV-seropositive participants:
- A dose-related increase in neutralizing antibody titers in both epithelial cell and fibroblast assays.
- In epithelial cells, the second vaccination boosted neutralizing antibody titers to a level of 10-fold to 19-fold baseline titers in all dose groups.
- In fibroblasts, the second vaccination boosted neutralizing antibody titers to a level of 2-fold to 4-fold baseline titers in all dose groups.
Safety and tolerability
A safety analysis showed that mRNA-1647 was generally well-tolerated. The most common local adverse event (AE) was injection site pain. The most common systemic AEs were headache, fatigue, myalgia, chills and fever. In general, systemic AEs occurred more frequently after the second dose and were more common in the seropositive cohorts compared to the seronegative cohorts.
The most frequent Grade 3 AEs in seropositive participants were myalgia (9-33% of a given dose cohort), chills and fatigue (9-27% of a given dose cohort) and fever (0-27% of a given dose cohort).
Of concern, there was a single Grade 4 AE of an isolated lab finding of elevated partial thromboplastin time (PTT), which was elevated at baseline (Grade 1) and self-resolved on the next lab test with no associated clinical findings. Since the possibility that this event was vaccine-related cannot be completely ruled out, investigators will look to the Phase 2 study to see if there is any evidence of elevated PTT in vaccinated individuals.
Taken together, these interim data from Moderna’s Phase 1 study of its mRNA-based CMV vaccine are encouraging since no candidate CMV vaccine to date has elicited comparable titers with the potential to block CMV transmission. We look forward to the publication of the full study results in a peer-reviewed journal.
In the meantime, based on these interim data, Moderna has said the company will soon start a Phase 2 study of mRNA-1647, reportedly in about 250 patients in the U.S., to confirm a dose for a pivotal Phase 3 study.
However, further studies will likely be needed to further assess the safety and efficacy of mRNA-1647 in different populations before embarking on a costly Phase 3 trial that would enroll thousands of subjects to prove the vaccine can prevent primary CMV infections.
In order to keep momentum going and move its ambitious development program forward, Moderna will doubtless be looking for partners to support the advanced development of mRNA-1647.
1 April 2019
It’s cherry blossom time and we’ve moved!
Washington, DC, April 1 – The Foundation has moved into beautiful new offices at 1717 Pennsylvania Avenue, near The White House. The move was fortuitously timed to coincide with the projected “peak bloom” of Washington’s famed cherry blossoms.
Our new home is in the heart of the nation’s capital, just one block west of the White House complex. From the rooftop terrace, The White House, the Old Executive Office Building, the Washington Monument and the World Bank are all visible from various vantage points, creating a spectacular panoramic view.
Fellow tenants include Fortune 500 government affairs offices, prestigious law firms, wealth management companies and government agencies. The neighborhood is also home to the international banking community, including the IMF and World Bank.
We hope you will come and visit us in our new home soon!
The Foundation for Vaccine Research
1717 Pennsylvania Avenue NW, Suite 1025
Washington, DC 20006
Tel +1 202 559 9062
5 March 2019
Foundation hosts Senate influenza briefing to support reintroduction of $1 billion Flu Vaccine Act
Washington, February 26. The Foundation for Vaccine Research, in partnership with the It’s Time Campaign and the Sabin Vaccine Institute, supported by Seqirus, hosted a special scientific briefing for Senators and their staff on the occasion of the reintroduction of the Flu Vaccine Act by Senator Edward J. Markey (D-Mass.) and Rep. Rosa DeLauro (D-CT).
Over the next 5 years, the legislation more than doubles U.S. investments in influenza vaccine research through the NIH. The money is designed to conduct or support comprehensive research for the creation of a universal influenza vaccine that could protect against multiple strains of the influenza virus and offer longer lasting protection.
The briefing was organized to conform with Senate ethics rules and held in the Senate Appropriations Committee Room in the Dirksen Senate Office Building. The 90-minute session was chaired by Dr. David Baltimore, Caltech, Pasadena, and the Foundation’s Board Chair, Prof. Simon Wain-Hobson, Institut Pasteur, Paris.
After welcome remarks by Sen. Markey and Rep. DeLauro, the briefing featured presentations by 8 leading influenza experts: NIAID Director, Dr. Anthony Fauci, followed by 4 speakers from academia: Drs. Florian Krammer (Icahn School of Medicine, Mt. Sinai), Ian Wilson (Scripps Research Institute), Scott Hensley (University of Pennsylvania), Jesse Bloom (Fred Hutch/University of Washington); and three R&D chiefs from industry: Drs. Gary Nabel (Sanofi), Kathrin Jansen (Pfizer) and Russell Basser (Seqirus).
The Flu Vaccine Act was formally reintroduced by Sen. Markey and Rep. DeLauro at 6:00pm ET on February 26, just hours after the briefing. The legislation calls for a total investment of $1 billion over 5 years – $200 million each year from FY 2020 to FY 2024 – in new money for the NIH.
Sen. Markey and his colleagues had previously been able to secure a dedicated $100 million and $140 million for FY 2018 and FY 2019, respectively, to boost universal influenza vaccine research at NIAID within NIH.
Senators co-sponsoring the Flu Vaccine Act are Tammy Baldwin (D-Wis.), Richard Blumenthal (D-Conn.), Angus King (I-Maine.), Tina Smith (D-Minn.), Chris Van Hollen (D-Md.), and Amy Klobuchar (D-Minn.).
A copy of the Flu Vaccine Act can be found HERE.
18 January 2019
New Brexit poll: UK would vote to stay in the EU by 12-point margin
LONDON, January 18 – Britain would vote to stay in the European Union by a 12-percentage point margin if the electorate were given another vote, according to a YouGov poll released yesterday. This would be the highest level since the June 2016 Brexit referendum.
The poll results showed that 56% of the UK would vote to stay in the EU and 44% would vote to leave, excluding those who would not vote or didn’t know. Among younger voters, over 80% would vote to remain.
Why this matters for vaccine research
Vaccine discovery and development depends on talent, resources and collaboration. Some of the brightest young and early-career scientists are based in the UK or started out there. Many of the best labs doing pioneering work in virology, immunology and vaccinology are in Britain, not just in Oxford, Cambridge and London. Two of the top five vaccine companies in the world are UK-based – GSK and Seqirus.
In the last 5 years, over half of the UK’s research output involved international collaboration, and 60% of that included EU partners. Leaving the EU would affect science funding and the mobility of scientists and their collaborations across the continent and diminish the country’s ability to influence policies and regulations that govern the international activities of science, the President of the Royal Society has said.
Vaccine research and development is no exception. As a global research enterprise, vaccine R&D requires collaborations with the United States, the European Union and numerous other worldwide partners.
The Foundation partnered with the Royal Society and the London School of Hygiene and Tropical Medicine for our first two overseas events. The first was a private screening for science writers of the movie “Contagion.” The second was the first international symposium on H5N1 at the Royal Society, for which the Foundation arranged financing.
In June 2016, the Foundation joined the scientific community in urging a Remain vote in the EU referendum on June 23. Leave won that vote by a margin of just four percentage points, 52% to 48%. Since then a growing majority of the electorate would choose to stay in the EU if given the chance in a second referendum – or a People’s Vote.
That’s why, with critical parliamentary votes ahead in the run-up to the March 29 deadline for exiting the EU, any one of which could stop or delay Brexit, the Foundation is proud to support the People’s Vote campaign and Scientists for EU.
Read statement from Dr. Venki Ramakrishnan, President of the Royal Society HERE
21 June 2018
Dr. Adel Mahmoud, FVR Board Director and tireless vaccine advocate, dies at 76
FVR Board Chair, Prof. Simon Wain-Hobson, writes:
Sadly, our good friend Adel Mahmoud passed away on June 11. Adel was a great teacher and mover, beloved by colleagues and everyone whose lives he touched. As president of Merck Vaccines, he played a pivotal role in bringing the rotavirus, HPV and shingles vaccines to market, as well as the quadrivalent measles-mumps-rubella-varicella (MMRV) vaccine. According to Merck, more than 500 million doses of these four vaccines have been distributed globally, saving hundreds of thousands of lives.
Our perspective is less well known. He was an active and unswerving supporter of the Foundation for Vaccine Research. On a rough day, Adel would always find a way to encourage, infecting us with his enthusiasm. He could be very down to earth. While recognizing the power of modern technology, he saw the disconnect between academic research and the grunt work necessary to producing a viable, robust vaccine. He was acutely aware that the list of diseases for which we do not have vaccines is longer than that for which we have vaccines. He insisted that vaccine research should be encouraged far more and was deeply frustrated by the West African Ebola epidemic of 2014.
The bitterness here was that there were Ebola virus vaccine candidates in the freezer. Stung by this, he joined with his longtime friend Stanley Plotkin in floating the idea of a fund that could push candidate vaccines for much needed diseases without a market into the clinic to be tested, a strategic goal of the FVR. This idea emerged in an important perspective published in The New England Journal of Medicine, joined by Jeremy Farrar, Director of the Wellcome Trust. This blossomed into the Coalition for Epidemic Preparedness Innovations (CEPI) that saw 2018 awards to two vaccine platforms for the testing of vaccine candidates for Lassa fever and MERS.
Adel was so very generous with his time and experience. Despite health problems over his last year, he was always available. Indeed, we had a meeting planned in his New York apartment on a Sunday the day before he died. He was very concerned that there was no good flu vaccine. The last twenty years or so haven’t brought any major advance and the seasonal vaccine last year was hopeless in adults aged 55+. His idea was to dream up a different way of approaching the problem for the modus vivendi clearly hasn’t come up with the goods. This was on the menu for the Sunday meeting that never happened. Speaking of which, he was generous to a T. He loved dining in company, flowers and music, to mention just three of his foibles.
As he was passionate about breaking the logjam around flu the FVR will try and do just that. It is the best we can do to honor a staunch vaccine advocate, mover and friend.
Prof. Simon Wain-Hobson
FVR Board Chair
Professor of Molecular Retrovirology
Institut Pasteur, Paris
31 March 2018
NIH wins $3 billion funding boost in 2018 omnibus spending bill
In a momentous outcome for supporters of biomedical research, NIH gains a budget increase of $3 billion over FY 2017 in the $1.3 trillion omnibus spending bill approved with bipartisan support on March 22 and signed by the president on March 23. The increase brings NIH’s total budget for FY 2018 to $37.1 billion. Research advocates had called for a $2 billon increase, the most they thought lawmakers would go for. As part of the package, CDC gets a $1 billion increase, bringing their budget for FY 2018 to $8.3 billion.
|FY 2017||FY 2018||$ increase||% increase|
|NIH||$34.1 billion||$37.1 billion||$3 billion||+9%|
|CDC||$7.3 billion||$8.3 billion||$1 billion||+14%|
The $3 billion boost for NIH represents a 9% increase over FY 2017, and exceeded expectations at a time when resources are scarce and the Administration has other priorities. Indeed, in a budget request submitted last May, the White House proposed a 17% reduction in NIH's budget for FY 2018, and indicated support for a cap on the portion of NIH grants that can be used to help cover research institutions’ facilities and administration costs.
The Foundation for Vaccine Research joined with 200 like-minded institutions in campaigning for the NIH funding boost as a member of the Ad Hoc Coalition for Medical Research. We would like to thank appropriators for their bold and visionary support, especially leaders of the House and Senate Appropriations Subcommittees with oversight of NIH funding, Chairmen Tom Cole (R-OK) and Roy Blunt (R-MO), and Ranking Members Rosa DeLauro (D-CO) and Patty Murray (D-WA).
The increase in funding for the NIH will bolster the nation’s unrivaled global leadership position in biomedical research and help maintain the agency's competitive edge at a time when other nations like China are increasing their investments in biomedical research.
The $37.1 billion approved by Congress for FY 2018 will serve as a new starting point for FY 2019 budget negotiations that are currently underway.
Securing a predictable funding stream
The increase in NIH funding continues a trend of substantial budget increases for the agency over the last several years despite perennial government budget concerns and spending caps. The goal of research advocates has been to secure a 5% annual budget increase for the NIH in order to maintain a sustainable, predictable funding stream for the agency, plus 2% to adjust for inflation and maintain the agency’s purchasing power.
The $37.1 billion includes the full $496 million for the 21st Century Cures Act program and $500 million split evenly between NINDS and NIDA for research related to opioid addiction.
Passage of the omnibus removes six months of uncertainty and flat funding for NIH after a series of fits and starts and stop-gap funding measures. The lifting of federal spending caps on February 7 enabled appropriators to work out budgets for all federal agencies based on new allocations. There is strong bipartisan support in Congress for increased U.S. investments in biomedical research. Increased funding for the NIH was never seriously in doubt.
The Consolidated Appropriations Act, 2018, the $1.3 trillion omnibus bill to fund federal discretionary spending programs through FY 2018, was approved by the House by 256-167 votes on March 22, and by the Senate by 67-30 votes on March 23.
“It is critically important to restore the purchasing power of the NIH which has been severely eroded in the past 10 to 15 years due to the soaring costs of biomedical research. An across-the-board 9% increase in the NIH’s budget for FY 2018 is most welcome but will do little on its own to reverse this decline. We should probably aim for annual increases of 10% or more in the years ahead to fully restore the NIH's purchasing power and maintain momentum.”
Prof. Adel A. Mahmoud, FVR Board Director
Department of Molecular Biology and
Woodrow Wilson School of Public and International Affairs
Former President, Merck Vaccines
31 March 2018
$100 million boost for universal influenza vaccine research
The FY 2018 omnibus bill includes $100 million in new money for NIH to advance the development of a universal influenza vaccine. This new funding, which was long advocated for by the Foundation, more than doubles the estimated $64 million that NIAID invested on universal influenza vaccine research in FY 2017.
In February, Senator Edward Markey (D-Mass.) introduced the “Flu Vaccine Act,” legislation to inject new momentum into the search for a universal influenza vaccine. The legislation called for a total investment of $1 billion over 5 years – $200 million for FYs 2019 through 2023 – towards his goal. The $100 million in the FY 2018 omnibus represents the first allocation to launch the initiative.
The funding boost comes at a time when the United States has been experiencing the worst influenza season since 2009 and news that this year’s flu shot is only 36% effective overall, according to interim CDC estimates released on February 15, 2018.
8 March 2018
CEPI awards $37.5 million to develop Lassa fever and MERS vaccines
The Coalition for Epidemic Preparedness Innovations (CEPI) and Austrian biotech Themis have announced a $37.5 million, 5-year partnership under which Themis will provide advanced development and manufacturing for a Lassa fever and a MERS vaccine.
The award is the first that CEPI has made since its formation in 2017 as a public-private partnership to finance and coordinate the development of new vaccines for rare diseases and infections with high outbreak and epidemic potential, but low market potential to interest large vaccine manufacturers. Lassa fever and MERS have been identified by CEPI as two of their highest priority diseases for which there are currently no licensed vaccines.
CEPI spun out of a high-profile initiative launched by the Foundation for Vaccine Research calling for a global vaccine development fund published in The New England Journal of Medicine in July 2015.
Both vaccines will use a novel 10-years-in-development, live attenuated, replicating measles vaccine platform developed by the Institut Pasteur in Paris, which licensed the platform to Themis.
CEPI’s investment represents an innovative approach to solving the challenge of advancing promising vaccine candidates through the so-called “Valley of Death” that has impeded the development of vaccines for diseases and infections that cause significant morbidity and mortality but have limited commercial prospects.
The money will be used to fund the development of Lassa and MERS vaccines from Phase 1 through Phase 2 human clinical trials so that vaccines are ready for efficacy studies during an outbreak.
Measles vaccine as a platform
The measles vaccine, one of the world’s safest and most effective vaccines used worldwide – usually as a component of the MMR vaccine – is an efficient, live attenuated, replicating virus that has been safely administered to 2 billion children over the last 40 years, affording life-long protection after a single dose. Taking advantage of these unique attributes, researchers at the Institut Pasteur in Paris transformed this attenuated measles virus into a versatile chimeric or recombinant vaccine vector with demonstrated proof-of-principle in humans and a preclinical track record of rapid adaptability and effectiveness for a variety of pathogens. Moreover, clinical trials have shown the safety and immunogenicity of this platform in individuals with preexisting immunity to measles.
Professor Frédéric Tangy heads the Viral Genomics and Vaccination unit in the Department of Virology at the Institut Pasteur in Paris that developed the live attenuated, replicating measles virus vaccine as a platform to develop new vaccines against Chikungunya, Dengue, SARS, MERS, Lassa fever and other emerging diseases and infections. The immunogenicity, safety, and tolerability of this strategy in humans was demonstrated in a first-in-man trial of a recombinant measles-virus-based Chikungunya vaccine (Ramsauer, et al., Lancet Infectious Diseases, March 2015).
“I was originally skeptical about the measles vector, but the results from the first human trials are impressive. A one-dose vaccine would be optimal for tropical diseases like Lassa fever. The latter will be a real test of the vector, as a T-cell response (as well as antibody) will be critical.”
Stanley A. Plotkin, MD
University of Pennsylvania
7 July 2017
Updated and expanded: Plotkin’s Vaccines, 7th Edition debuts on the world stage
Acclaimed by vaccine professionals the world over, the latest edition of the planet’s most authoritative and respected reference tome on vaccines and their use packs decades of knowledge and hard-won experience in one handy volume. First published in 1988 and updated every four to five years since, the launch of the 7th Edition marks another milestone in the impressive trajectory of Vaccines to become the undisputed leader in its field.
Vaccines has been the brainchild of Dr. Stanley Plotkin, a fact acknowledged by rebranding the book Plotkin’s Vaccines. The 1st edition, which was intended for researchers, public health officials and health workers who vaccinate, was published by Saunders and counted 633 pages and covered 26 vaccines. As one measure of how the field has exploded in the last three decades, the 7th Edition has more than 1,500 pages and covers 54 vaccines.
Over the years, editing Vaccines has become a collaborative effort. Among giants in the field who have made important contributions are Dr. Walt Orenstein, Emory University (starting with the 3rd edition), Dr. Paul Offit, Children’s Hospital of Philadelphia (starting with the 5th edition), and Dr. Kathryn Edwards, Vanderbilt University (who joined the team for the 7th edition).
Plotkin’s Vaccines, 7thEdition, encapsulates in one opus everything that a professional needs to know about vaccines and how they should be used. Available now, the book can be ordered online from the publisher, Elsevier, or from medical bookstores everywhere. Free digital version is included with print purchase.
“My hope is that this expanded edition of Vaccines will inspire a generation of younger scientists to enter the field of vaccinology and engage in the discovery and development of critically needed new vaccines with the potential to make a positive impact on global public health.”
Stanley A. Plotkin, MD
University of Pennsylvania
“Providing the knowledge needed for evidence-based decision-making is critical to expanding immunization and ensuring that life-saving vaccines are used correctly. Here we have an indispensable tool and reference work for training immunization managers, doctors, nurses and health workers who vaccinate, as well as a resource for public health officials and policy makers charged with drafting guidelines for vaccine use and the establishment of policies that support vaccination and improve immunization outcomes. Turning vaccines into vaccination is one of our greatest challenges. Getting vaccines from where they are manufactured to where they are most needed and can be used correctly doesn’t happen without attention to every detail. The last mile is often the longest mile. The critical information contained in this book will help health professionals, communities and countries make better informed decisions for that last mile.”
Bruce G. Gellin, MD, MPH
President, Global Immunization
Sabin Vaccine Institute
Former Deputy Assistant Secretary for Health
Director, National Vaccine Program Office (2002-2017)
U.S. Department of Health and Human Services
Plotkin’s Vaccines, 7thEdition, runs 1,504 pages and boasts roughly 20% new material. The number of chapters has been expanded from 78 to 82 since the 6th edition, divided into five sections:
- General aspects of vaccination
- Licensed vaccines and vaccines in development
- New technologies
- Vaccination of special groups
- Public health and regulatory issues
Section 2 comprises the bulk of the book (70%) with 54 chapters, each devoted to a specific disease or infection, from adenovirus to Zika. Each in-depth chapter runs an average of 20 pages. New to the 7th Edition are a description of all Ebola vaccines in development, the latest information on recently-licensed vaccines for dengue, cholera, zoster, meningococcal group B, and the enterovirus 71 vaccine licensed in China. The section also contains new recommendations and changes to polio vaccines.
Each chapter contains vital information for each disease, including clinical characteristics, microbiology, pathogenesis, diagnosis, and treatment; epidemiology; and public health and regulatory issues – plus complete information for each vaccine, including its stability, immunogenicity, efficacy, duration of immunity, adverse events, indications, contraindications, precautions, administration with other vaccines, and disease-control strategies. Also included in this section is an analysis of the cost-benefit and cost-effectiveness of different vaccine options. The section also features a new chapter on maternal immunization.
Recognizing that researchers, doctors, nurses, students and health workers are constantly on the move and may not have the time or inclination to lug around a hefty 8.3 lb. book, Plotkin’s Vaccines, 7th Edition, is also available in an electronic version, which is included with the purchase of the print edition. The Expert Consult™ eBook version has been enhanced to allow users to search all of the text, figures, and references from the book on a variety of devices, according to the publisher.
In such a fast-moving field with so many promising new vaccines in development and being licensed for use, there is growing support in the research community for updating the online version of the book. Dr. Plotkin has urged the publisher to consider such updates whenever there is a major new development, such as the licensure of a new or improved vaccine that would change or supersede recommendations in the book. While Elsevier does not currently have a process for updating content online they are reportedly investigating the possibilities.
Vaccines has become the standard reference and an indispensable tool for researchers and decision makers worldwide interested in and committed to preventing disease. However, the recommended retail price (US$360.00 for the print + eBook, US$323.00 for the eBook alone) would seem to put the book out of reach for many people in developing countries who could benefit the most from the information contained in it and where it will have the greatest public health impact.
In response to an inquiry, Elsevier says individual countries will discount for their markets by 20% or more, and in the absence of an actual International Edition (a version sold at a specific discounted price for certain markets), they will try to work with the territories to help them with their individual market needs. A quick survey reveals that a resourceful shopper in a major market like India or China can purchase the book for less than US$300.00.
In what they are billing as a “Limited-time summer sale,” Elsevier itself is offering the print +eBook at a 25% discount for U.S. customers if purchased directly from the publisher: for US$270.00 instead of $360.00. Look for future special offers on their website.
More information and how to order can be obtained from Elsevier
5 June 2017
Vaccine discovery will suffer if proposed cuts to the NIH’s FY 2018 budget are enacted
Just when research advocates thought that things could not get worse, the Trump administration has proposed a draconian $7.2 billion (21%) cut to the NIH’s budget for FY 2018. A cut of that magnitude would be unprecedented in the agency’s history, cripple biomedical research, thwart scientific progress, and hamper the discovery and development of critically needed vaccines.
The Trump administration released its full budget proposal on May 23. It provides a program level of $26.9 billion for the NIH in FY 2018, a $7.2 billion (21%) cut below the final FY 2017 in the omnibus spending bill. If enacted by Congress, the cut would lead to 2,000 fewer grants being awarded compared to FY 2016. It would also wipe out the hard-fought gains of recent years and reverse the trajectory of steady, predictable funding for the NIH with modest increases each year to adjust for inflation.
The proposal stands in harsh contrast to the $2 billion increase called for by the Ad Hoc Group for Medical Research, of which the Foundation is a member. On May 23, the same day the proposal was released, the group fired back and put out a statement, backed by full-page ads in The Wall Street Journal and Politico, thanking Congress for their support of medical research and calling again for a $2 billion increase for the NIH in FY 2018.
The Foundation is grateful to Congress for their support of vaccine research and biomedical research in general and looks forward to working with members to develop a sensible, clear-eyed, forward-looking budget that will provide the NIH with the predictable, sustainable funding that it needs to build on scientific advances.
Read the full story
“I can say NIH will remain a priority in my budget, and we’re going to do everything we can to stay on the course we’re on — which is predictable and modest increases in funding.”
Rep. Tom Cole (R-OK), Chairman, House Appropriations Labor-HHS Subcommittee, when asked for his reaction to the proposed NIH budget cuts on May 23
“Are we ready to abdicate our role as a world leader in research? Hard-won advances in biomedical and biological research pay off. Federally-funded research has provided better health, enhanced our quality of life and brought greater understanding of the causes of rare diseases. Never have our opportunities for additional progress been greater, but if we want to continue this success, it requires sustained and predictable growth in the nation’s research funding.”
Hudson H. Freeze, PhD President, Federation of American Societies for Experimental Biology
Impact of proposed cuts
The chart opposite shows the dramatic impact of the proposed $7.2 billion cut to the NIH's budget in FY 2018, in current and constant dollars. The consequences would be severe, immediate and far-reaching, affecting thousands of scientists who rely on NIH grants to support their work, and be felt across America with no region or program spared. The reduction would not only reverse the trend towards setting the NIH on a sustainable trajectory but also undo the hard work undertaken by Congress in securing additional funding for NIH via the 21st Century Cures Act.
Leaders in the biomedical research community and research advocates have called on Congress to immediately reject the administration’s budget proposal, describing the proposed cuts as “outrageous, unconscionable and unjustified.” The sentiment was shared by many members of Congress who were equally dismayed.
On May 24, Senators Bob Casey (R-PA) and Richard Burr (R-NC) sent a letter to the Senate Appropriations Committee asking them to “maintain a strong commitment to funding for the NIH in the FY 2018 Labor-HHS bill.” The letter, which was signed by 57 Senators (15 Republicans, 40 Democrats, 2 Independents), noted the recent support provided by Congress to the NIH and stated that the U.S. “must continue to invest in biomedical research that has the potential to save money in the future, improve the lives of Americans, and offer an economic return for our Nation.”
The Senate letter follows a compelling March 31 letter sent to the House Appropriations Committee signed by 206 House Republicans and Democrats, urging appropriators to consider an increase of “at least $2 billion over FY 2017 for the NIH in FY 2018 to reflect the rising costs of biomedical research.” The requested increase was deemed "the minimum level of funding to reflect the rising costs associated with biomedical research," according to the four House members, Representatives David McKinley (R-WV), Susan Davis (D-CA), André Carson (D-IN), and Peter King (R-NY) who championed the initiative.
Raising the debt ceiling
Among the many daunting political challenges, distractions and competing priorities facing the Trump administration is the urgent need to raise the federal debt ceiling. Appropriators have started to craft their annual spending bills for FY 2018 without knowing how much money they have to play with, thanks to a budget process that is seriously behind schedule. Adding to the pressure, lawmakers are in session for just three more months before the September 30 deadline.
Moreover, top White House advisers appear divided on the need to raise the debt ceiling. Budget Director Mick Mulvaney and Treasury Secretary Steve Mnuchin are reportedly not in agreement, with Mnuchin calling for a clean debt ceiling hike, and Mulvaney pushing for further spending reforms. If lawmakers cannot reach agreement by summer’s end, the country faces the prospect of a government shutdown, sequestration, which would freeze budgets for FY 2018 at FY 2017 levels, or a continuing resolution, as witnessed in the battles over this year’s budget.
The uncertainty caused by the debt ceiling battles only adds to the uncertainty which is already beginning to take its toll on the morale of NIH staff and scientists who depend on the NIH for funding.
12 MAY 2017
FY 2018 outlook: Many uncertainties ahead
After last week’s good news which saw the omnibus spending bill for FY 2017 (HR 244) signed into law with $34.1 billion for the NIH, a $2 billion (approx. 6%) increase over last fiscal year, advocates for biomedical research are gearing up for the next challenge: securing another robust increase for NIH in FY 2018 to develop a sustainable and predictable funding stream for the agency.
For multiple reasons, budget negotiations for FY 2018 are expected to be much tougher than last year. For starters, the Administration is proposing a $5.8 billion cut (approx. 18%) to the NIH’s budget for FY 2018. Even if Congress ignores the Administration's proposal to cut NIH funding, as they just did for the current fiscal year, the cap on FY 2018 non-defense discretionary spending (NDD) is $3 billion lower than the cap for FY 2017. Unless a deal is cut to increase the FY 2018 cap, the prospects for maintaining NIH funding at the current level, let alone securing another increase to keep pace with inflation, are dim.
Special challenges for Congress include how to handle competing priorities, such as boosting defense spending and paying for proposed tax cuts, the probable need for sequestration relief, tensions on the Hill, and the fact that budget negotiations are seriously behind schedule.
Despite these challenges, the Foundation remains optimistic that lawmakers will maintain their strong commitment to funding for the NIH in FY 2018, with an appropriate increase to adjust for inflation.
To achieve the goal of securing long-term, predictable, inflation-adjusted funding for the NIH, the Ad Hoc Coalition for Medical Research, of which the Foundation is a member, has proposed a funding level for the NIH in FY 2018 that is at least $2 billion above FY 2017, in addition to funds included in the 21st Century Cures Act for targeted initiatives. Such an increase would compensate for inflation and help maintain the budget trajectory.
The “skinny budget” released by the White House in mid-March proposed a $5.8 billion cut (approx. 18%) in NIH funding for FY 2018. The proposal drew immediate bipartisan opposition and stands little chance of being approved by legislators, according to Hill watchers. In an impressive show of support, 206 members of the House of Representatives signed a March 31 letter to the House Appropriations Committee in which they urged appropriators to consider an increase of at least $2 billion for the NIH in FY 2018 “to reflect the rising costs of biomedical research.” Senators Bob Casey (D-PA) and Richard Burr (R-NC) are currently circulating a similar letter urging the Senate Appropriations Committee to “maintain a strong commitment” to funding for NIH in FY 2018.
The NIH is the crown jewel in the U.S. biomedical research enterprise. It is the engine that drives biomedical research and an engine for economic growth, as both parties recognize. Despite strong Congressional support for biomedical research, budget negotiations for FY 2018 that start again in earnest next week are expected to be a long-drawn-out affair with many uncertainties.
Outlook for vaccines
Vaccine research accounts for between 6% and 7% of biomedical research funded by the NIH, extramurally and intramurally. This level of support has remained fairly constant over the years, and includes money for HIV, TB and malaria vaccine research, as well as other priority targets, such as respiratory syncytial virus (RSV), which can be serious, especially for infants and older adults.
As we saw during the Ebola, MERS and Zika outbreaks, NIH funding for vaccine research can surge during public health emergencies, although the additional funds needed to develop vaccines were hard to secure quickly. Like all biomedical research, vaccine research benefits from long-term, predictable, sustainable funding in order to be prepared for future public health emergencies which are sure to occur.
In recent years, NIH support for vaccine research has become more important as vaccine manufacturers have increasingly come to rely on vaccine discovery funded by the NIH intramurally or extramurally by grants to academia and biotechs. Most vaccine discovery these days springs from university and biotech labs, not from pharma. Any reduction in NIH support would impact the pace of vaccine discovery, development and licensure.
Moreover, there would be a multitude of unintended consequences of any draconian cut to the NIH budget. If the proposed $5.8 billion cut were adopted, there could be a loss of nearly 90,000 jobs in the U.S. and $15 billion in economic activity, according to an independent think tank. NIH-funded research in 2016, conducted at academic and medical institutions in every state in the nation, directly and indirectly supported 380,000 jobs across America and contributed $65 billion in economic activity.
This is a continuing story and will be updated.
5 MAY 2017 - 3:30 PM
BREAKING NEWS: Trump signs omnibus spending bill
President Trump has signed into law the $1.1 trillion omnibus appropriations bill that cleared both houses of Congress earlier this week, Principal Deputy White House Press Secretary Sarah Huckabee Sanders said at a White House press briefing Friday. Trump signed the bill behind closed doors at his home in central New Jersey, well ahead of a midnight Friday deadline.
The spending package provides $34.1 billion for the NIH in FY 2017, a $2 billion increase over last year. Advocates will now turn their attention to advocating for a similar increase in FY 2018 to maintain this level of spending for the NIH, adjusted for biomedical research inflation, fending off a proposed $5.8 billion cut to the NIH budget next year. Budget negotiations for FY 2018 are expected to restart on May 15 when Congress returns from their one-week break.
4 MAY 2017 - 2:15 PM ET
THIS JUST IN: Senate approves spending bill by 79-18 votes. The bill now heads to the president's desk.
3 May 2017 - 4:30 pm ET
BREAKING NEWS: House passes spending bill
In an impressive show of support for biomedical research, the House of Representatives has approved a $1.1 trillion spending package for FY 2017 that provides $34.1 billion in funding for the National Institutes of Health, a $2 billion boost over last year. The bill easily passed the House with support from both parties in a 309-118 vote. The legislation now heads to the Senate, where it is expected to be approved as early as tomorrow and signed by President Trump before a Friday deadline.
The Foundation for Vaccine Research commends the House of Representatives for approving the spending bill with a $2 billion increase for the NIH, and calls upon the Senate and President Trump to follow suit and finalize this investment without further delay.
The NIH funding level in the omnibus continues a budget trajectory for the world’s leading biomedical research agency at a time of unparalleled scientific opportunity. Ensuring steady, sustainable budget growth for the NIH that accounts for inflation will help accelerate the development of critically needed new vaccines, as well as other interventions that can save millions of lives.
1 May 2017
Bipartisan agreement reached to increase NIH funding for balance of FY 2017
Congressional leaders late on Sunday reached a bipartisan agreement on the outline of a deal to fund the government through September, ensuring uninterrupted funding for the NIH and ending any suspense about the possibility of a government shutdown on May 5, after Congress granted itself a one-week extension.
The bipartisan agreement, which still must be voted on by lawmakers, is testimony to the strong support for increased U.S. investments in biomedical research. The bill provides a total of $34.1 billion for the NIH in FY 2017, $2 billion above the FY 2016 enacted level, despite the Administration’s request that its budget be cut by $1.2 billion for the rest of the fiscal year. The spending package, if approved, would be the first significant bipartisan measure approved by Congress during the Trump presidency.
The Foundation for Vaccine Research applauds leaders of the U.S. House and Senate Appropriations Committees for persevering in their support of a continued robust investment in the NIH in FY 2017, building on their success in FY 2016. In particular, we commend Senate Labor-HHS-Education Appropriations Subcommittee Chair Sen. Roy Blunt (R-MO) and Ranking Member Sen. Patty Murray (D-WA), and House Subcommittee Chair Tom Cole (R-O.) and Ranking Member Rosa DeLauro (D-CT), for continuing the longstanding bipartisan, bicameral tradition of championing the national commitment to medical research.
Reaction to the landmark bipartisan agreement reached on Sunday has been swift and uniformly positive. We urge the vaccine research community to contact their members of Congress to vote for the FY 2017 omnibus spending bill and ensure that it becomes a reality. The House is expected to vote on the measure as early as May 3, with the Senate to follow. Then lawmakers will turn their attention to plans for FY 2018. Success this year puts down a marker and enhances the prospects of continued bipartisan support for U.S. investments in biomedical research next year.
This story was updated on May 2.
“With the amazing advances in biomedical science, we have never been in a better position to make great medical advances. If there has ever been a time to invest in this promise, now is the time. Public funding of science, through the NIH, has been one of the great innovations and success stories of the last 50+ years. In my own field, viral hepatitis, we have seen amazing progress – from the discovery of a widespread human pathogen to new treatments that can cure almost everyone with minimal side effects. This would not have been possible, or at least greatly delayed, without intramural and extramural NIH funding. This enterprise, which fuels the majority of biological research in our country, is however fragile. Cutting, rather the increasing the NIH budget, would do irreparable harm and almost certainly presage a loss of U.S. competitiveness. If you care about your children, your grandchildren and future generations, this is where we should invest, not cut. A quote by Lewis Thomas, from a piece he wrote for the Lasker Foundation over 30 years ago, is as true today as it was then: “In the course of scientific progress, things tend to pop up. Most of the celebrated achievements had their origins in moments of surprise in the laboratory, unplanned for, unanticipated, unpredicted. No committee convened [ ] to survey the future prospects for biomedical research could possibly have guessed at the things that lay ahead. No branch of government could have laid out detailed plans for the scientific needs of the future, beyond asserting [ ] that what the country needed was more fundamental knowledge about the human form and function, about the agents and influences responsible for disease, and, in a certain sense, about nature itself. Scientific research works, it is the only way to get at the underlying mechanisms of disease, and the only way to learn what to do about them.”
Charles M. Rice, PhD Maurice R. and Corinne P. Greenberg Professor in Virology The Rockefeller University Lasker Award, 2016 Robert Koch Prize, 2015
10 April 2017
Lawmakers oppose NIH budget cuts, urge increased investment instead
In an impressive show of bipartisan support, 206 House Republicans and Democrats joined together on a March 31 letter to the House Appropriations Committee in which they urged appropriators to consider an increase of at least $2 billion over FY 2017 for the NIH in FY 2018 to reflect the rising costs of biomedical research.
According to the authors, a modest increase of that amount, which accounts for inflation, is the minimum level of funding needed to reflect the rising costs associated with biomedical research. If enacted, such an increase would bring the NIH budget for FY 2018 to at least $36 billion. Reps. David McKinley (R-WV), Susan Davis (D-CA), André Carson (D-IN), and Peter King (R-NY) championed the initiative.
This bipartisan effort was followed by an April 3 letter to Office of Management and Budget Director, Mick Mulvaney, by Reps. Fred Upton (R-MI), former Chairman, House Committee on Energy and Commerce, and Committee member, Diana DeGette (D-CO), in which they made an impassioned appeal for increased investment in the NIH and voiced their opposition to the administration’s proposed budget cuts in FY 2017 and 2018.
This support for the NIH was echoed by powerful House and Senate appropriators whose leadership may be decisive. Interviewed for an April 6 article in the McClatchy Washington Bureau, Appropriations Committee Chairmen, Sen. Roy Blunt (R-MO) and Rep. Tom Cole (R-OK), who have been actively advocating for an increase in appropriations for the NIH, said they will push for Congress to increase the NIH’s annual $32 billion budget.
The two veteran Republican lawmakers aim to convince the White House to join their efforts to boost NIH spending by at least $20 billion over the next 10 years. The total annual budget for NIH by the end of that period would then be about $50 billion.
If they succeed, it would represent a complete reversal of the White House’s position last month when the administration asked for $5.8 billion in cuts to the NIH’s FY 2018 budget, an 18% decrease, plus $1.2 billion in cuts to the agency’s FY 2017 budget.
This growing bipartisan support for the NIH from Congressional leaders bodes well for the tough budget negotiations that must take place immediately after the Spring recess. The deadline to reach agreement on the final spending bill for FY 2017 is May 28.
"This is not a partisan issue. Disease isn’t Democratic or Republican. Congress voted to reinvest in NIH research because we recognize its remarkable return on investment for the American people, and so we oppose any cuts to the NIH budget in FY17 or FY18. NIH research saves lives, creates jobs, controls long-term entitlement costs, protects our national security, and advances our global leadership, all while bringing renewed hope to patients and families across the country."
Rep. Fred Upton Former Chairman, House Committee on Energy & Commerce Rep. Diana DeGette Member, House Committee on Energy & Commerce in April 3 letter to Office of Management and Budget Director, Mick Mulvaney
“Over many decades, modern vaccines have averted millions of premature deaths and saved billions of dollars. As new infections, such as Zika, emerge, the capacity to respond and create effective vaccines is a top priority for health security. To reduce NIH funding and other support for the basic and biomedical science that underlie vaccine development and deployment would be penny wise and pound foolish. Even worse, such misguided reductions would leave everyone vulnerable to avoidable illness and misery.”
Harvey V. Fineberg, MD, PhD
President, Gordon and Betty Moore Foundation
President, Institute of Medicine (2002-2014; now National Academy of Medicine)
"In this critical time of converting scientific breakthroughs into translational advances in biomedicine, a cut in NIH funding would have the devastating effect of inflicting maximum damage with minimum gain. If the federal government pulls back further from an already flat funding landscape for biomedical research, it will also send a chilling message to our steadily dwindling pipeline of early career researchers and scientists who represent our best hope for the future of healthcare in the United States."
Robert Tjian, PhD University of California, Berkeley President, Howard Hughes Medical Institute (2009-2016)
“The Administration wants to boost defense spending to enhance our national security but seems to have lost sight of the greatest national security threat of all: our fight against infectious disease. To pay for the increases, they have proposed cutting back many federal programs, including those that prepare us to wage the war against microbes, the most lethal enemy we are ever likely to face. This is where “defense spending” needs to be boosted. There is no more powerful weapon in our human arsenal against infectious diseases than vaccines. Now is the time to make the world more secure, and that starts with maintaining and ideally increasing our investments in all aspects of vaccine research, development, licensure, manufacturing and deployment.”
Michael T. Osterholm, PhD, MPH Regents Professor McKnight Endowed Presidential Chair in Public Health Director, Center for Infectious Disease Research and Policy University of Minnesota
28 March 2017
NIH funding: White House proposes new sweeping budget cuts
In a surprise move described as more March madness by one lawmaker, the Trump administration has proposed slashing the NIH budget by another $1.2 billion, this time for the current fiscal year, FY 2017.
The proposed cut is part of a $18 billion package of spending reductions sought by the administration for the current fiscal year which ends September 30. It follows the administration's March 16 proposal to slash NIH funding by $5.8 billion in FY 2018, a plan that was met with fierce resistance from outside groups, biotech leaders and many members of Congress.
The proposed $1.2 billion cut to this year’s NIH budget mainly targets research grants. The reduction would more than wipe out the $1.1 billion that Congress approved last September to combat Zika and continue work on the development of a Zika vaccine.
The cuts are likely to be rejected by Congress where there is strong bipartisan support for the NIH and biomedical research in general.
Lawmakers on both sides of the aisle are already panning the proposal, particularly after the bipartisan success of the 21st Century Cures Act signed into law last December, which aimed to boost biomedical research innovation through $4.8 billion in new funding for the NIH over 10 years. Asking representatives to vote against the same research center they just funded will be a hard sell.
Congress ultimately decides the federal government’s spending priorities. The government is currently being funded by a stopgap measure called a continuing resolution (CR) passed by the Senate in December 2016, which expires on April 28, 2017. Budget negotiations on the supplemental appropriations bill put forward by the administration for the balance of FY 2017, which includes the proposed spending cuts to the NIH, will need to come to a head before then in order to avoid a government shutdown.
The Foundation urges Congress to enact without further delay a final FY 2017 spending package that includes the Senate Appropriations Committee-approved $34.1 billion for the NIH and to ensure that NIH remains a top investment priority in FY 2018 and beyond. Prioritizing a budget trajectory for NIH that advances sustainable, predictable growth is essential to ensuring America's continued leadership in vaccine R&D – and securing our children's future.
This is a developing story and will be updated.
"As a virologist, my passion has always been to seek to understand the fundamental biology and ecology of these unique microbes. I strongly believe that this knowledge will lead not only to discoveries we cannot anticipate, but also to improvements in health of the flora and fauna that inhabit our planet. There is a larger view as well because history teaches us that economic stability is interwoven with scientific progress. It is distressing to realize that the current administration is ignoring this important lesson. Instead of cutting back on science funded by the NIH for example, we should be strengthening our discovery infrastructure and our public health programs. A major cutback of NIH support will affect not only the current generation of scientists, it also will have a devastating effect on future generations who will be shut out of a research career. Reducing the investment in research support is short sighted and a very steep and slippery slope from which there are no good outcomes."
Lynn Enquist, PhD
Henry L. Hillman Professor of Molecular Biology
Professor, Princeton Neuroscience Institute
Past President, American Society for Microbiology
“The NIH, with its ability to identify promising ideas across the universe of scientific discovery, plays a singular role in global health R&D. As the HIV vaccine field looks to the future, we are increasingly aware of the need for scientific knowledge from partners working on a range of issues that can speed progress toward a vaccine. With breadth like no other scientific organization, NIH can draw on insights generated in one field that have unexpected—and critical—applications in another. Diminished research support will thwart this productive collaboration and upend years of progress. The toll that will take on our ability to conquer life-threatening diseases, including HIV/AIDS, is hard to imagine and impossible to quantify.”
Mark Feinberg, MD, PhD
President & CEO
International AIDS Vaccine Initiative (IAVI)
16 March 2017
NIH would see huge budget cut under president’s proposal
The NIH would be hit with a $5.8 billion cut under President Trump’s first budget proposal for FY 2018 unveiled today, about 18% of its current $32 billion budget.
The cut to the crown jewel of U.S. biomedical research – long recognized as an engine for economic growth – confirmed NIH watchers’ worst fears. The 18% decrease is at the high end of estimates put together by budget experts, according to insiders familiar with the process.
If enacted across the board, the proposed cut of 18% magnitude would impact all areas of biomedical research funded by the agency, including the roughly $2.2 billion invested each year by the NIH in critically-needed vaccine research.
There is no mention in the president’s proposal of the CDC’s budget for FY 2018. If there are also going to be cuts in the CDC budget, the effect on vaccination could be devastating.
Under President Obama, the NIH received a funding boost of $2 billion for FY 2016, and another cash infusion for FY 2017, when $6.3 billion in new funding for the 21st Century Cures Act, which includes former VP Joe Biden’s Cancer Moonshot initiative, sailed through Congress with strong bipartisan support.
President Trump’s budget proposal would reverse this trend of increased support for the NIH in dramatic fashion.
It runs counter to calls to increase the NIH budget, including one by Newt Gingrich, former speaker of the House, less than two years ago, in which he called for doubling the NIH budget.
It also runs counter to suggestions by leading lawmakers in the House that they would call for a $2 billion increase for NIH for FY 2018.
Read the full story
"I find it hard to improve on what Newt Gingrich wrote two years ago. 'When it comes to breakthroughs that could prevent or cure diseases, government is unique. It alone can bring the necessary resources to bear. The federal government funds roughly a third of all medical research in the United States. And it is ultimately on the hook for the costs of illness. It’s irresponsible and shortsighted, not prudent, to let financing for basic research dwindle.' To which I can only add, funding for NIH and CDC should be priorities. Disease has a negative economic effect. Conversely, good public health is positive for the American economy."
Stanley A. Plotkin, MD
FVR Board Director
Emeritus Professor of Pediatrics
University of Pennsylvania
See further comment
"Science has taken us out of the Age of Darkness and into the Age of Enlightenment. Because of science, we live 30 years longer than we did a hundred years ago. Cutting back on science funding is, at best, shortsighted. And, as is always true, it will be our children and their children who will suffer our ignorance."
Paul Offit, MD
FVR Board Director
Maurice R Hilleman Professor of Vaccinology
Co-inventor of the rotavirus vaccine
and Professor of Pediatrics
The Children's Hospital of Philadelphia
"A recent analysis of the impact of 13 vaccines universally recommended for children in the U.S. reported that routine childhood immunization will prevent about 42,000 early deaths and 20 million cases of disease, with net savings of $13.5 billion in direct costs and $68.8 billion in total societal costs, respectively. Development and licensure of those vaccines is based on substantial investments in basic scientific research to understand what constitutes an effective immune response, and how do we safely induce it. Much of that funding comes from the NIH. There are unfortunately many more infectious diseases for which we need vaccines, and investing in the research to develop them must be a top priority. Support for NIH is absolutely critical if we are to make more progress and improve our health and the health of our children.”
Walter A. Orenstein, MD
Former director of the U.S. National Immunization Program
Associate Director, Emory Vaccine Center
Professor of Medicine, Pediatrics and Global Health
Emory University, Atlanta
"A substantial NIH budget cut would [...] erode America’s leadership in medical research; and it would diminish opportunities to discover new ways to prevent and treat diseases. [...] As I have learned from my own time at the NIH, this is not about Republicans versus Democrats. It is about a more fundamental divide, between those who believe in evidence as a basis for life-altering and nation-defining decisions and those who adhere unflinchingly to dogma. It is about a conception of national leadership that connects our economic success and our security to the generation of knowledge, and to the arts and sciences, not just to our military strength. […] In confronting the president’s assault on the NIH, all members of Congress face a moment that will define their character and the future of the country."
Harold E. Varmus, MD, PhD
Professor, Weill Cornell Medicine
Former NIH Director, 1993 to 1999,
writing in The New York Times, March 22
Drastic cut in spending
Reducing the NIH budget by $5.8 billion as proposed by the Administration would reduce the agency’s FY 2017 budget from roughly $32 billion to just under $26 billion in FY 2018, wiping out the hard-fought gains achieved in the past decade and a half.
As shown in the graph opposite, the proposed $5.8 billion cut would bring the NIH budget down well below the 2003 level, as measured in current dollars. As if that were not alarming enough, in constant, inflation-adjusted dollars, it would bring the agency’s budget down to under $13 billion, a level not seen since 1998.
Put another way, under the proposal the NIH would be expected to operate in FY 2018 on a little more than the same budget that it enjoyed 20 years ago. The proposed cut would dramatically accelerate the decline in the agency’s purchasing power witnessed since 2003. It also throws into sharp relief the perils of putting out blueprint budgets without fully considering the consequences.
For Congressional budget historians, the proposed $5.8 billion cut, if enacted, would far exceed the sequestration cuts that the NIH had to absorb in 2013. As previously mentioned, it also goes against the intent of the bipartisan $2 billion increase that Congress provided to the NIH in FY 2016, and a similar amount that was approved by the Senate Appropriations Committee last summer.
What's at stake
The NIH funds research into a vast array of diseases and conditions, including cancer, heart disease, and infectious diseases. More than 80% of the NIH's funding is awarded through almost 50,000 competitive grants to more than 300,000 researchers at more than 2,500 universities, medical schools, and other research institutions in every state and around the world.
It is widely considered the crown jewel of biomedical research in the world.
About 10% of the NIH's budget supports projects conducted by nearly 6,000 scientists in its own laboratories, most of which are on the main NIH campus in Bethesda, Maryland. Its world-renowned clinical center treats patients from around the globe seeking last-chance cures and volunteers testing cutting-edge therapies.
The biomedical and health-related research programs housed and conducted on the NIH campus in Bethesda – which include the National Institute of Allergy and Infectious Diseases (NIAID), home to the Vaccine Research Center, the National Cancer Institute, and 24 other institutes – employ 18,000 people, all of whom would almost certainly be affected by a budget cut of this magnitude.
A cut of the proposed size would prove highly disruptive to that research, whether it is applied across the board or to some grants only.
It is hard to overestimate the negative impact of the proposed budget cut on all biomedical research programs funded by the NIH, extramurally and intramurally. Many vital research programs would have to be cut back. Many others may have to be curtailed. It is to be hoped that sounder minds will ultimately prevail.
This story was updated on March 23.
28 February 2017
BARDA’s Richard Hatchett named to head CEPI
It was announced today from Oslo that Richard J. Hatchett, MD, has been named CEO of CEPI, the Coalition for Epidemic Preparedness and Innovations launched last August.
As reported January 19, CEPI seeks to raise $1 billion over the next 5 years to develop vaccines against three emerging infectious diseases – Lassa fever, Middle East Respiratory Syndrome (MERS), and Nipah virus infection.
Dr. Hatchett joins CEPI from the U.S. Biomedical Advanced Research and Development Authority (BARDA) at the U.S. Department of Health and Human Services (HHS), where he served as Chief Medical Officer and Deputy Director.
He will lead CEPI through its crucial next development phase, which includes finding a permanent home for the organization – with London rumored to be the frontrunner – and overseeing implementation of the group’s ambitious R&D plans and first investments.
Over the course of his career, Dr. Hatchett has led medical countermeasure development programs at BARDA and at the U.S. National Institutes of Health (NIH).
He has played leading roles at HHS in designing these programs, as well as planning for and responding to the H5N1 avian influenza ("bird flu") scare, the 2009 H1N1 influenza pandemic, and the Ebola, MERS, and Zika epidemics.
Before joining BARDA in 2011, he served as Director for Medical Preparedness Policy on the White House National Security Staff under the Bush and Obama Administrations.
Known for his diplomatic and personal skills, Dr. Hatchett is a graduate of Vanderbilt University, majoring in English, and the Vanderbilt University Medical School. He completed a residency in Internal Medicine at New York Hospital – Cornell Medical Center, and a fellowship in Medical Oncology at Duke University Medical Center.
He starts in his new position as CEPI CEO in mid-April 2017, based in Oslo initially.
This story was updated March 2
25 February 2017
Potential paradigm shift in the making: Novel vaccine that targets mosquito saliva debuts in human phase 1 trial
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has launched a phase 1 clinical trial to test a novel vaccine concept designed to provide broad protection against a range of mosquito-transmitted diseases, such as Zika, malaria, West Nile virus and dengue fever.
Developed by London-based biotech SEEK, the vaccine, which is called AGS-v, targets mosquito saliva instead of the virus or parasite carried by mosquitoes. If successful, this novel approach would represent a game changer in the fight against mosquito-borne diseases. It could also be adapted to prevent other vector-borne illnesses, such as leishmaniasis which is transmitted by sandflies.
The phase 1 study – the first saliva-based human vaccine trial of its kind – is being conducted at the NIH Clinical Center in Bethesda, Maryland, led by Dr. Matthew J. Memoli, director of the Clinical Studies Unit in NIAID’s Laboratory of Infectious Diseases.
The double-blind, placebo-controlled study will enroll up to 60 healthy volunteers to examine the vaccine’s safety and ability to generate an immune response. The first six volunteers were vaccinated last week.
What the experts say
“It is exciting to see an alternative vaccine strategy debut in a human clinical trial where a mosquito salivary component is used as the antigen instead of the conventional pathogen component. Testing a mosquito salivary protein as a potential vaccine in humans will open the door for testing salivary proteins from other key disease vectors, such as sandflies that transmit the parasite that causes leishmaniasis.”
Jesus G. Valenzuela, PhD
Chief, Vector Molecular Biology Section
Laboratory of Malaria and Vector Research
National Institute of Allergy and Infectious Diseases, NIH
“The development of a saliva-based vaccine to prevent a mosquito-borne disease would represent a profound paradigm shift in how we go about developing vaccines against malaria, dengue, Zika, West Nile virus, and other mosquito-transmitted infections. An all-purpose vaccine of this sort – if born out in proof-of-concept trials – would underscore the scientific merit of trying radically new approaches to developing vaccines for the most challenging targets – even if the new approach challenges established dogma.”
Prof. Simon Wain-Hobson, FVR Board Chair
Chief, Molecular Retrovirology
Institut Pasteur, Paris
“This phase 1 clinical trial was pulled together rapidly in response to the emergence of Zika. It is more ambitious in its scope than a typical phase 1 study as it is designed to include the examination of the vaccine's effect on humans and mosquitoes. Fortunately we were working with SEEK on another trial when this novel vaccine approach was brought to our attention. When we realized the enormous potential of an all-purpose vaccine that would protect against many mosquito-borne diseases, our interest was spiked. We shall see if our excitement is justified in the months ahead.”
Matthew J. Memoli, MD
Director, LID Clinical Studies Unit
Viral Pathogenesis and Evolution Section
Laboratory of Infectious Diseases
National Institute of Allergy and Infectious Diseases, NIH
"A universal vaccine that protects against all mosquito-borne diseases and infections would be a real game changer, if proven to be safe and effective in subsequent studies. Such a multi-purpose vaccine would have an immense impact on global public health and help save hundreds of thousands of lives, especially children who are sickened and can die from malaria and other mosquito-transmitted diseases and infections every year."
Paul Offit MD
Maurice R Hilleman Professor of Vaccinology
Co-inventor of the rotavirus vaccine
and Professor of Pediatrics
The Children's Hospital of Philadelphia
About the vaccine
Unlike other vaccines which target specific mosquito-borne pathogens, the AGS-v vaccine is designed to trigger an immune response to mosquito saliva. Experiments have shown that saliva is necessary for blood feeding, but the saliva also changes the immunological environment of the skin. This immunological change permits viruses and parasites to gain a foothold when injected by mosquitoes.
Indeed, a peculiarity of mosquito transmission seems to be that molecules injected by mosquitoes are absolutely essential for viruses to get established, and probably needed for parasites to gain a foothold. Moreover, there’s tantalizing evidence that the same is true for other pathogens transmitted by sandflies and other insects.
The experimental AGS-v vaccine contains four synthetic proteins that mimic proteins found in mosquito salivary glands. The proteins, which are highly conserved across all mosquito species, have been shown to be safe in animal studies, and are designed to induce an immune response in vaccinated individuals that can prevent infection when a person is bitten by a disease-carrying mosquito.
The study protocol calls for up to 60 healthy volunteers to be randomly assigned to receive one of three vaccine regimens. The first group will receive two injections of the AGS-v vaccine, 21 days apart.
The second group will receive two injections of AGS-v combined with an adjuvant, 21 days apart. The third group will receive two placebo injections of sterile water, 21 days apart. Neither the study investigators nor the participants will know who is assigned to each group.
Participants will be asked to return to the clinic twice between vaccinations and twice after the second vaccination to undergo a physical exam and to provide blood samples. Study investigators will examine the blood samples to measure levels of antibodies triggered by vaccination and T-cell responses of stimulated PBMCs.
Each participant also will return 21 days or so after completing the vaccination schedule to undergo a controlled exposure to biting mosquitoes. The mosquitoes will not be carrying viruses or parasites, so the participants will not be at risk of becoming infected with a mosquito-borne disease. Five to 10 female Aedes aegypti mosquitoes from the insectary in NIAID’s Laboratory of Malaria and Vector Research will be put in a feeding device that will be placed on each participant’s arm for 20 minutes. The mosquitoes will bite the participants’ arms through the netting on the feeding device.
Afterward, investigators will take blood samples from each participant at various time points to see if participants experience a modified response to the mosquito bites as a result of AGS-v vaccination.
Study investigators will also examine the mosquitoes after feeding on vaccinated individuals to assess any changes affecting their life cycle or their fitness to feed and replicate, which would be a huge added bonus.
Scientists suspect that mosquitoes who take a blood meal from vaccinated individuals may have altered behavior – perhaps by ingesting antibodies when they feed – that could lead to early death or a reduced ability to reproduce. This would suggest the vaccine could also hinder disease transmission by controlling the mosquito population.
All study participants will be asked to return to the clinic at the NIH Center for follow-up visits every 60 days for five months following the mosquito feeding. A final clinic visit to assess long-term safety will take place about 10 months after the mosquito feeding.
The NIH-funded study is expected to be completed by summer 2018.
21 February 2017
Ebola funding surge masks falling investments in neglected diseases
Research funds for global diseases and infections are at their lowest levels for a decade, if money for Ebola research is excluded, according to the annual G-FINDER report by Policy Cures Research, a health policy analysis group in Sydney, Australia.
Global funding for research on neglected diseases – which include HIV, TB and malaria – is at its lowest level since 2007. But that total – just over US$3 billion for 2015, the latest year for which figures are available – does not include a rapid burst of funding for research into Ebola to tackle the outbreak in West Africa. Investments in Ebola and other African viral hemorrhagic fevers, like Lassa fever, shot up to $631 million in 2015, more than was spent on any other neglected disease except HIV.
The steady decline in spending for diseases other than Ebola can be attributed to a fall in public funds from high-income countries, such as the U.S. and UK, according to the report, which was funded by project partner, the Bill & Melinda Gates Foundation.
“The only encouraging take-away from this report is that rich countries are prepared to significantly increase their investments in vaccine research when confronted by a health emergency. Even that takes some prodding, as we saw with Ebola and Zika. When an outbreak is particularly scary like Ebola, or is deemed to have epidemic potential like MERS, the funds can usually be found, even if everyone has to scramble. This is short-sighted. Investing in global health security and vaccine development should be a public health priority. The benefits of investing in R&D accrue to all and cannot be overestimated.”
Prof. Adel A. Mahmoud, FVR Board Director
Department of Molecular Biology and
Woodrow Wilson School of Public and International Affairs
Former President, Merck Vaccines
Highlights of the report
By design, the annual G-FINDER survey tracks public, private and philanthropic investments in R&D for global diseases and infections that disproportionately affect people in developing countries, and that don't have enough of a commercial market to attract much private R&D.
Research funding for all neglected diseases, as defined by the G-FINDER team, excluding Ebola and other VHFs, amounted to just over $3 billion in 2015, a decrease of 2.3% from the previous year.
As before, the big three or “top tier” diseases – HIV, TB and malaria – received the vast majority of global R&D funding ($2.1million, 71%), which was down approx. 3% from the previous year.
Funding for “second tier” diseases, a vast and diverse group that includes many of the nastiest tropical diseases that are a significant cause of morbidity and mortality in developing regions, fell by approx. 6% overall. The group, referred to somewhat blandly as “Other” in the figure opposite, includes diarrheal diseases, kinetoplastid diseases (such as African sleeping sickness, Chagas disease, leishmaniasis), dengue, bacterial pneumonia and meningitis, helminth infections (schistosomiasis, lymphatic filariasis, river blindness, hookworm, tapeworm, and roundworm), salmonella and hepatitis C.
While funding for this tier was down by 6% overall, the trend was highly uneven. For example, funding for kinetoplastid diseases as a group was down by 18%, diarrheal diseases down 11%, hepatitis C down 25%, and helminths down 13%. By contrast, funding for dengue was up 14%, as was bacterial pneumonia and meningitis up 12%, and salmonella infections up 3%.
Funding for “third tier” diseases, the most neglected of the neglected – leprosy, cryptococcal meningitis, trachoma, rheumatic fever, Buruli ulcer and leptospirosis – each received less than 0.5% of global R&D funding, which is hard to explain when compared to the $631 million poured into Ebola R&D in 2015.
Almost two-thirds of funds invested in Ebola was spent on vaccine development, and more than one-third came from industry. That is an unusually high proportion, according to team leader Dr. Nick Chapman. “At the same time that we’re seeing this huge explosion in Ebola funding, governments are letting funding slide for other neglected diseases,” Chapman says.
Rich countries accounted for 97% of the $1.9 billion in public funds for R&D in 2015. Much of the U.S. money was delivered through grants from the National Institutes of Health, meaning that neglected disease R&D is vulnerable to funding changes at the agency.
Philanthropic funding fell slightly in 2015. The two main donors, the Bill & Melinda Gates Foundation and the Wellcome Trust, together accounted for 95% of the $645 million invested by the sector in 2015. The Wellcome Trust cut its investment for neglected diseases research by 33% since 2012, according to the report.
The highly concentrated nature of neglected disease R&D funding remains an area of concern, according to the study authors. Researchers and developers continue to rely upon a small number of large funders, particularly the U.S. government and its agencies (the NIH especially) and the Bill & Melinda Gates Foundation.
While investments in R&D for global diseases and infections are not yet in actual free fall, declining investment trends are a cause for concern if Ebola is excluded. The numbers for 2016 when they are in can be expected to follow trend. However, the outlook for 2017 is distinctly less clear. This can be attributed to political uncertainties, and the tendency of rich countries to only increase spending in response to emergencies such as Ebola and Zika.
20 February 2017
Bill Gates issues warning about dangers of genetic engineering to create a highly contagious and deadly flu strain
Speaking before 500 security experts in Munich last week, Bill Gates Jr., co-founder of Microsoft and chair of the Bill & Melinda Gates Foundation, who has invested billions of his own money in a drive to improve health worldwide, warned that we ignore the link between health security and international security at our peril.
Expanding on his theme, Gates told his audience that “the next epidemic has a good chance of originating on a computer screen of a terrorist intent on using genetic engineering to create a synthetic version of the smallpox virus or a contagious and highly deadly strain of flu.” He added, “epidemiologists show through their models that any respiratory-spread pathogen would kill more than 30 million people in less than a year, and there is a reasonable probability of that taking place in the years ahead.”
We couldn’t agree more.
"Many experts concerned about global health security have been trying to draw attention to this issue for some years now. It is extremely gratifying to see a world leader of Bill Gates's stature bring this before the Munich Security Conference."
Tom Inglesby, MD
Director, Johns Hopkins Center for Health Security
Johns Hopkins Bloomberg School of Public Health
FVR leadership on this issue
The views expressed by Gates about the wisdom of making pathogens more dangerous are shared by many concerned scientists.
The Foundation for Vaccine Research and its Board Chair, Professor Simon Wain-Hobson, took an early lead on this issue, writing opinion pieces for The Financial Times, Nature, EMBO Molecular Medicine, penning letters to Science and other journals, and petitioning U.S. federal agencies and commissions, backed by a concerted PR campaign winning editorials in The New York Times and other leading newspapers.
The FVR partnered with the Royal Society in April 2012 and co-organized the first international symposium on the topic, “H5N1 research: biosafety, biosecurity and bioethics,” and helped organize a similar high-level symposium with the Volkswagen Foundation in Hanover, Germany, in December 2014, “Dual use research on microbes: biosafety, biosecurity, responsibility.”
FVR experts participated in numerous workshops in the U.S. and Europe on what came to be known as “gain-of-function” research. Highlights include testifying before the Biological Weapons Convention Conference in Geneva, the U.S. National Science Advisory Board for Biosecurity (NSABB) at the NIH, and the European Academies Science Advisory Council (EASAC); speaking at workshops hosted by the U.S. National Academy of Sciences, the Royal Society, and the Royal Netherlands Academy of Arts and Sciences; granting TV and radio interviews; and organizing private briefings on the topic in Washington DC and elsewhere.
6 February 2017
Vaccines for HIV and TB: The defining challenge of our time.
The search for HIV and TB vaccines are the holy grails for vaccine developers. Between them, they are responsible for 2.8 million deaths globally each year, according to the WHO. They are two of the highest priority diseases for which we still do not have effective vaccines.
The BCG vaccine is more than 90 years old and is only partially effective. It can protect against childhood invasive TB, but has little or no effectiveness against the more common pulmonary TB in adults.
After three decades of trying, we still don’t have a vaccine to prevent HIV infection. A phase 3 trial of a modified, two-vaccine regimen used in the Thai trial, RV144, is under way in South Africa, but significant efficacy of any HIV vaccine has yet to be demonstrated.
The limited progress being made reinforces concerns about whether conventional approaches will work for HIV and TB. Many scientists believe new ideas are needed, and that these may well come from outside the field.
In the months ahead, the Foundation for Vaccine Research will be launching a series of initiatives to refocus attention on HIV and TB and help mobilize the resources needed to imagine new paths for a vaccine.
24 January 2017
Big pharma launches a multimillion-dollar TV ad campaign in pushback on drug pricing concerns
The Pharmaceutical Research and Manufacturers of America (PhRMA), the Washington lobbying group that represents the pharmaceutical industry, yesterday launched a massive TV image-building campaign designed to influence public opinion and shift the debate about drug prices to one about medical breakthroughs that can lead to cures and save lives.
The campaign debuted on the first full workday of the new Administration amid growing calls for action on escalating drug prices. Whether lawmakers will be swayed by the emotional impact of the campaign to tread softly on drug prices remains to be seen.
Vaccines have not experienced the same price hikes as some medicines, and so do not seem to be in the firing line at present. Some industry analysts consider that vaccine makers are protected to a certain degree in the current debate.
Having said that, everyone who believes in vaccines should push back harder against groups who seek to create doubts about vaccine safety. Vaccines have an equally compelling success story to tell, and advances in science and technology promise an equally bright future. A similar campaign should be considered to get the vaccine message across.
23 January 2017
Phase 2 trial of radiation-attenuated malaria vaccine debuts in Kenya
A phase 2 study launched today in Siaya County in Western Kenya marks a major advance in the development of a radiation-attenuated whole sporozoite malaria vaccine. Sanaria’s PfSPZ Vaccine has been shown to be safe and well tolerated in 14 completed and ongoing phase 1 and 2 clinical trials conducted in the U.S., Germany and several African countries, among more than 800 healthy volunteers ranging in age from 5 months to 65 years of age.
The phase 2 trial will assess the safety, tolerability and protective efficacy of the vaccine administered by direct venous inoculation (DVI) to infants 5-12 months of age, living in an area of high-malaria transmission. The hope is the vaccine will show high-level sterilizing protection for at least 1 year, according to study sponsor Sanaria. This would provide an important and necessary step toward gaining regulatory approvals for the vaccine.
The study, the largest to date of PfSPZ Vaccine, is being conducted in collaboration with the Kenya Medical Research Institute (KEMRI) and the U.S. Centers for Disease Control and Prevention (CDC), with financial support from the Vaccine Research Center, NIAID, NIH.
Among the different vaccine approaches being tested to prevent malaria infection, whole Plasmodium falciparum sporozoite vaccines have shown consistent, high-level protection in a number of clinical trials reported in Science, Nature Medicine and other journals (see links below). A major focus of the last 10 years of malaria vaccine research has been to determine whether live-attenuated whole sporozoite malaria vaccines are safe and effective and can provide long-lasting protection against P. falciparum.
There are three methods used to attenuate P. falciparum sporozoites for vaccination purposes: attenuation by radiation, attenuation using antimalarial drug treatment, and genetic attenuation (see our January 9 story on the results of a phase 1 trial of a triple-gene knockout live-attenuated malaria vaccine). The majority of data in humans to date with injectable sporozoite vaccines has been with radiation-attenuated vaccines.
Sanaria’s vaccine consists of aseptic, purified, cryopreserved, radiation-attenuated P. falciparum sporozoites, which when given by direct venous inoculation (DVI) to malaria-naïve volunteers in the United States were shown to be safe and well tolerated. The vaccine showed dose-dependent, protection up to 14 months after the final immunization against controlled human malaria infection. The tolerability and safety of PfSPZ Vaccine by DVI is further supported by a series of clinical trials conducted in 4 sub-Saharan countries (Mali, Burkina Faso, Equatorial Guinea, and Tanzania) and Germany in multiple age groups.
Protection against heterologous challenge
An important aspect of a successful malaria vaccine will be to confer protection against a variety of different P. falciparum strains. Results from a phase 1 study conducted by scientists at the U.S. Naval Medical Research Center and the Walter Reed Army Institute of Research (WRAIR) demonstrated that PfSPZ Vaccine can confer short-term protection against controlled human malaria infection with a heterologous strain in malaria-naive adult subjects. The findings were published January 2017 in the journal JCI Insights. These data have been substantiated in a further study that will soon be published. Together, these findings along with studies in Africa provided the foundation for developing an optimized immunization regimen for preventing malaria that is the focus of the present study among infants in Kenya.
Kenya phase 2 trial
The primary purpose of the phase 2 study is to measure the safety, immunogenicity and efficacy of PfSPZ Vaccine when given to infants from 5-12 months of age, inclusive. The double-blind, randomized, placebo-controlled trial will enroll ~400 infants. Volunteers will be randomized to one of three different dose arms or to a placebo group. The trial’s primary efficacy endpoint will be to assess protective efficacy during a 6-month follow-up period after the final vaccination. The secondary endpoint will be to assess efficacy after 12 months. The study will take 2 years to complete.
Fast-track review status
In September 2016, Sanaria won fast-track review status for PfSPZ Vaccine at the FDA, which could speed its path to licensure. Scientific and financial support has been received from multiple divisions at NIAID, NIH, and the U.S. Department of Defense and multiple other institutions worldwide organized into the International PfSPZ Consortium.
Equatorial Guinea trial
While the phase 2 trial is being conducted in Kenya, plans are being finalized to conduct a pivotal phase 3 clinical trial of PfSPZ Vaccine in Equatorial Guinea, backed by $48.5 million in funding. The government of Equatorial Guinea will invest $36.75 million. Marathon Oil, Noble Energy, and AMPCO, will provide $11.75 million. Their contribution marks the first time that oil companies with large workforces in malaria-endemic areas will help fund a large-scale clinical trial of a malaria vaccine. It is anticipated that the phase 3 trial could start as soon as 2018 or early 2019.
19 January 2017
Coalition announces financial commitments of $460 million in Davos
CEPI, the Coalition for Epidemic Preparedness Innovations, today announced $460 million in financial commitments at the annual World Economic Forum in Davos, Switzerland. Formed in August 2016, CEPI aims to raise $1 billion over the next 5 year to develop vaccines against three emerging infectious diseases – MERS, Lassa fever, and Nipah virus.
The Wellcome Trust and the Bill & Melinda Gates Foundation are backing the effort with $100 million each spread over 5 years. The governments of Japan, Germany, and Norway have pledged to contribute an additional $260 million over a similar period.
CEPI morphed out of an initiative launched by the Foundation for Vaccine Research in July 2015 with publication of a paper in The New England Journal of Medicine authored by the FVR’s Stanley Plotkin and Adel Mahmoud, as well as Wellcome’s Jeremy Farrar, calling for a global vaccine development fund that would also cover endemic and neglected diseases.
9 January 2017
Triple gene knockout revives prospects for a live-attenuated malaria vaccine
Results of a phase 1 study of a genetically-attenuated malaria vaccine published in Science and Translational Medicine showed that the vaccine was safe and well tolerated, opening up a third potential pathway to the development of a whole parasite vaccine via the creation of live-attenuated parasite strains using gene deletions.
The triple gene knockout worked as designed in its first human clinical trial, causing neither malaria nor serious safety problems in the 10 people who volunteered to be infected by mosquitoes. It also stimulated an immune response that holds out promise of a more protective vaccine than the single malaria candidate vaccine, RTS,S, now in pilot roll-out studies.
The live-attenuated parasite vaccine was created by scientists at the Seattle-based Center for Infectious Disease Research (CIDR), which pioneered the creation of genetically-attenuated Plasmodium parasites. The phase 1 study was conducted by scientists at CIDR and Fred Hutchinson Cancer Research Center, with support from U.S. Army.
“These are early days, yet results of our phase 1 study raise hopes that a genetically-attenuated whole parasite malaria vaccine might be an effective means by which we can prevent infection, and maybe one day help to eradicate malaria. Human challenge trials scheduled to start June/July will provide more data on the safety and efficacy of this approach.”
Stefan Kappe, PhD
Professor and Director for Translational Science
Center for Infectious Disease Research
Affiliate Professor, Department of Global Health
University of Washington
Malaria is caused by the Plasmodium falciparum parasite and spreads to humans through the bite of an infectious mosquito. With 5,300 genes and a life cycle that involves multiple stages in humans and mosquitoes, the Plasmodium parasite is far more complex than disease-causing viruses, complicating efforts to develop a vaccine against it.
Transmission occurs through the bite of an infected female Anopheles mosquito and the resulting deposition of a relatively small number of Plasmodium sporozoites into the skin of the host. Sporozoites traverse numerous cells in the skin before entering the bloodstream and rapidly going on to infect hepatocytes. The sporozoites then transform into liver stages of the parasite, which go on to replicate within the liver without causing symptoms, generating tens of thousands of new forms of the parasite that exit the liver and infect red blood cells. Infection of red blood cells is cyclical and rapidly expands the parasite population, causing the classic fever, chills, headaches and other malaria-associated symptoms that can lead to death in babies, young children and adults. Studies conducted in a mouse model with a human liver suggest that effectively targeting the pre-erythrocytic sporozoite and liver stages by vaccination could cripple the parasite, preventing disease and death and, as a bonus, prevent onward transmission.
The gene knockout concept
The notion of using genetically-attenuated malaria parasites as a vaccine to prime the immune system has long intrigued scientists and has been extensively explored in rodent malaria models. The discovery of numerous gene knockouts that arrest parasite development at critical points during liver infection in the mouse led to the creation of the first dual gene deletion strain of Plasmodium falciparum. Of all Plasmodium species that infect humans and animals, P. falciparum is the deadliest human malaria parasite. It is responsible for 75% of malaria cases – and nearly all deaths – in sub-Saharan Africa.
The deletion of two genes in P. falciparum, Pf. p52 and Pf. 36, expressed in the “pre-erythrocytic stage” of the parasite’s life cycle had been shown in an earlier phase 1 study to severely cripple the parasite but did not achieve complete attenuation in human infection. The two genes regulate sporozoite infectivity for mammalian hosts before red blood cells are infected, including factors that are critical for parasite liver infection and liver stage growth.
To see if the deletion of a third gene expressed during the same stage of the parasite’s life cycle could achieve full attenuation, scientists went on to create a triple gene deletion strain of P. falciparum by knocking out an additional gene in the SAP1 locus shown to be essential for successful liver stage infection in rodent malaria parasites.
Results from a second phase 1 study conducted in 2015 and reported last week in Science and Translational Medicine showed that the addition of a third gene deletion maintained immunogenicity and achieved full attenuation. The triple gene knockout permanently and uniformly crippled the complex malaria parasite so that it cannot go on to infect red blood cells and cause disease and, instead, effectively primes the immune system, reviving hopes that a genetically-attenuated parasite vaccine is a feasible alternative.
RTS,S subunit vaccine
The most clinically advanced malaria vaccine candidate to date is GSK’s subunit (whole protein) vaccine, RTS,S/AS01, which targets the host immune response through production of antibodies to a major P. falciparum sporozoite surface protein, the circumsporozoite protein (CSP), which mediates protection by preventing infectious sporozoites from reaching the liver. A large phase 3 clinical trial with RTS,S showed some efficacy against clinical malaria infection. However, such protection was short-lived and well below the goal of 75% set forth by the WHO, even after four immunizations. Nevertheless, the data that partial pre-erythrocytic immunity can reduce clinical malaria episodes were the first evidence for any efficacy by a malaria vaccine, raising hopes that generating a higher degree of sterilizing pre-erythrocytic immunity by vaccination could not only prevent disease and death but also contribute to elimination of malaria.
Whole sporozoite vaccines
Numerous pre-clinical and clinical studies have demonstrated that immunization with whole malaria sporozoite vaccines can confer complete, sterilizing immunity against malaria infection. Such vaccines likely mediate protection by generating a high frequency of T cell responses in the liver. Moreover, an important feature of whole sporozoite vaccines is their ability to generate responses to multiple antigens, providing breadth of immunity. There are currently three approaches using whole sporozoite vaccines.
The most widely-studied immunization strategy is with radiation-attenuated sporozoites, in which parasites are subjected to random irradiation-induced DNA damage, thereby preventing parasite replication in the liver. In a number of clinical studies in the U.S. and Africa, radiation-attenuated sporozoites have been shown to be very safe and well tolerated. Moreover, durable protection has been observed up to 1 year following 3 immunizations administered by direct venous inoculation in malaria-naïve adults. Based on these data, there are ongoing studies in Africa to determine if this vaccine approach confers sterilizing protection in infants and adults.
Concurrent administration of antimalarial drugs
A second strategy is immunization with live, infectious sporozoites and the concurrent administration of antimalarial drugs, which allows for completion of liver infection and eliminates asexual parasites once they initiate replication within red blood cells. This method requires about 20-fold fewer sporozoites to induce complete protection but is limited by the need to provide continuous antimalarial drug cover during immunization. Ongoing studies using drug therapy that can be administered only at the time of immunization with the live sporozoites will determine if this is safe and the vaccine remains protective.
The third strategy, immunization with live sporozoites that can self-attenuate in vivo, provides potentially the optimal approach for safety, efficacy and efficiency. Accordingly, scientists in Seattle developed a way to weaken the live malaria parasite in vivo by knocking out three genes that the organism needs to replicate in the human liver and re-emerge in the bloodstream to cause illness. The use of a genetically-attenuated parasite marks the first time that genetic engineering has been used to combat any parasitic disease. From a safety standpoint, this live-infection vaccine approach would self-attenuate in the liver and not require any drug treatment. In terms of vaccine efficacy, a critical aspect is where in the liver the live sporozoites attenuate. Pre-clinical data suggest that if the attenuation occurs late in the liver stage, protection is improved. In this regard, it would mimic the efficiency of the live-infection vaccine without the need for drug treatment.
The Seattle study
In the phase 1 triple gene knockout trial, the safety and immunogenicity of the genetically-engineered sporozoites were tested in 10 human volunteers using infected mosquito bites with a single exposure consisting of 150 to 200 bites per subject. All subjects remained blood stage-negative and developed inhibitory antibodies to sporozoites.
The phase 1 study focused on safety and immune responses. It did not directly test whether the immune responses that were elicited actually protected against malaria infection. Now that the approach has been shown to be safe, the next step will be a full efficacy evaluation in a controlled human challenge trial planned for later this year. The new trial will deliver the attenuated parasites to volunteers and then expose them to a strain of malaria that is easily diagnosed and responds to conventional antimalarial treatment.
For the moment, the triple gene knockout sporozoites can only be produced in the salivary glands of mosquitoes. So in the trial, each of the 10 volunteers placed their arms over a net-covered cup of mosquitoes and endured 150 to 200 bites in one 10-minute session.
Once safety and protective efficacy is established, the next critical step is to isolate the sporozoites from the mosquito so they can be enumerated and frozen for use in a vaccine study, an approach that has been done for irradiated sporozoites. The ultimate goal will be to perfect a manufacturing approach so the sporozoites can be grown to scale in vitro without the mosquito. There is existing data for doing this but it will require refinement. Developing a better – and more comfortable – delivery method will be a high priority. Down the road, the large-scale production of genetically-attenuated sporoziotes may prove to be an even greater challenge since no one has yet found a way to mass produce sporozoites in the quantities that would be needed for a mass vaccination campaign.
In the meantime, there are few places in the world that can do the controlled human challenge trial planned for later this year. CIDR’s Human Challenge Center, which is based at the Fred Hutchinson Cancer Research Center in Seattle and run by CIDR, is one of only four places in the U.S. – and the only non-military center – with an “insectary” for breeding malaria-carrying mosquitoes. The Hutch also conducts malaria human challenge trials that deliver malaria sporozoites – the infectious form of the parasite ordinarily introduced into human blood by a mosquito’s bite – via direct venous inoculation.
This approach developed by Sanaria, a biotech in Rockville, MD, could offer a more practical and more scalable delivery method down the road. The biotech has also developed the technology to grow and harvest large quantities of purified Plasmodium sporozoites and formulate them for use in vaccines for human use, as well as genetically-attenuated sporozoites as immunogen to be used in live-attenuated vaccines.
22 December 2016
Ebola experimental vaccine provides 100% protection, study shows
Final results from the Guinea "ring vaccination", open-label, cluster-randomized trial published in The Lancet show an rVSV-vectored vaccine to be highly effective in preventing Ebola infection. Of nearly 6,000 volunteers vaccinated with the vaccine, all were free of the virus 10 days later. In a group of the same size not vaccinated, 23 later developed Ebola disease.
The experimental vaccine, rVSV-ZEBOV, is a recombinant, replication-competent vesicular stomatitis virus-vectored vaccine expressing a surface glycoprotein of Zaire Ebolavirus. Originally developed in Canada but now owned and manufactured by Merck, the vaccine is currently being fast-tracked for approval by U.S. and European regulatory agencies.
The Guinea trial, dubbed “Ebola Ça Suffit!” – which translates as “Ebola, enough already!” – was conducted by the World Health Organization in cooperation with the Guinea Ministry of Health, with financial support from the Wellcome Trust, Médecins Sans Frontières, the Norwegian Ministry of Foreign Affairs, and the Canadian Government.
There are multiple strains of Ebolavirus, and this vaccine covers the Zaire group and offers cross-protection for similar strains in this group, according to the WHO. But it doesn't confer protection from four other strains of Ebolavirus known to cause disease in humans: Sudan Ebolavirus, Taï Forest Ebolavirus (formerly Côte d'Ivoire Ebolavirus), and Bundibugyo virus (Bundibugyo Ebolavirus), nor from the related, and lethal, Marburg virus.
The rVSV-EBOV vaccine is expected to be available by 2018, if not before. Spurred by the success of this vaccine, work developing vaccines for the four other Ebolavirus strains will hopefully accelerate, as well as for Marburg virus.
Where there's a will...
“The results of the Guinea ring-vaccination trial show what can be done in an emergency despite the obstacles when everybody pulls together. With an effective vaccine – hopefully soon be registered – the world will be prepared to respond immediately to any new outbreak of Ebola Zaire.”
Marie-Paule Kieny, PhD
Health Systems and Innovation
World Health Organization
15 December 2016
Obama signs 21st Century Cures Act
Paying tribute to both bipartisanship and his vice president, Joe Biden – who was galvanized by his own son’s death to change the way the United States combats cancer – President Obama this week signed a landmark $6.3 billion bill to boost spending for medical research, speed the development and approval of experimental treatments, and overhaul federal policy on mental health.
Two years in the making, the bipartisan measure was approved in the U.S. Senate by an overwhelming 94-5 vote last week after passing the House of Representatives by a similar margin. The bill provides an infusion of $4.8 billion for the NIH for biomedical research, including a hefty $1.8 billion for cancer research, a part of the bill that was renamed the “Beau Biden Cancer Moonshot” by lawmakers in honor of the vice president’s son who died of a brain tumor. Of the balance, $500 million was set aside for the FDA to help speed the approval of drugs, with a further $1 billion in grants destined for states to battle the opioid crisis and address mental health challenges.
While vaccines are not included in the bill, the legislation should provide encouragement to advocates of increased U.S. investments in vaccine R&D by showing how bipartisan support can be mobilized to address the funding chasm that is impeding the development of critically needed new vaccines.
"The Cures Act is a rare example of a concerted bipartisan effort to secure increased funding for promising areas of biomedical research with the potential to change the lives of thousands of Americans. While there is no money in it for vaccine research, the Act could serve as a model for bipartisan collaboration on an initiative to address the funding chasm that is impeding the development of urgently needed, life-saving vaccines for which there is no obvious market potential."
Prof. Adel A. Mahmoud, FVR Board Director
Department of Molecular Biology and
Woodrow Wilson School of Public and International Affairs
Former President, Merck Vaccines
14 December 2016
GSK opens new global vaccines R&D hub in Rockville, MD
Seeking to “walk the talk” with global biopreparedness efforts, GlaxoSmithKline yesterday cut the ribbon on its sparkling new Rockville, Maryland, vaccines R&D hub, welcoming research partners to its antibody-shaped campus outside of Washington, DC.
The new facility will serve as a dedicated location for the discovery and development of vaccines to prevent potential deadly disease outbreaks as GSK continues to push the conversation about creating a global network with other organizations and governments. The opening marks a another step forward in the development of the company’s proposed “Biopreparedness Organization.”
Confirming GSK’s ambitions in the field, CEO Andrew Witty said that the Rockville site can hopefully serve as a “node on a network of nodes” to create a much safer position for future threats after Ebola and Zika caught the scientific community off guard in recent years.
But getting buy-in from other stakeholders has been tough to attain. “Everybody we talked to loves it,” said Moncef Slaoui, GSK chairman of vaccines. “But we have been talking about it for two years and two months. It’s progressing very slowly because there are so many stakeholders involved. It’s a little frustrating, I must say, but we will continue and will be persistent.”
Witty said that in each recent outbreak, the global reaction has been "worse than the previous response.” The company is hoping to end that pattern with a move to "walk the talk" with a physical contribution to work in disease areas that might otherwise be neglected.
Rockville will be the home of GSK’s proposed “Biopreparedness Organization” (BPO), which the company conceives as a dedicated, permanent organization using a "no profit/no loss" model that will design and develop new vaccines against emerging viruses, bacteria and other pathogens that potentially pose a threat to global public health.
The new facility will employ 450 scientists and support staff – creating up to 200 new jobs – and house 12 critical vaccine development programs. In addition to biopreparedness, scientists at the site will conduct research in commercial vaccine areas. These include the further development and support for its candidate shingles vaccine, which was filed for FDA approval in October, as well as R&D programs for respiratory syncytial virus (RSV), Group B Streptococcus, and dengue which will be based at the site.
GSK acquired the Rockville site in 2012 when it bought Human Genome Sciences for $3 billion. The company says it will invest over $50 million in the next two years to continue to develop the site with latest state-of-the-art scientific research technology and equipment.
Rockville sits just outside Washington, DC in close proximity to the NIH, FDA, BARDA and other potential partners. The NIH recently signed on with the company to work on Zika. The Rockville site becomes one of three global vaccines R&D hubs for GSK, complementing the company’s existing global R&D centers in Rixensart, Belgium and in Siena, Italy.
6 December 2016
International Vaccine Institute invests $34 million in Inovio’s MERS vaccine
New funding via the International Vaccine Institute (IVI) in Seoul, South Korea, made possible by a $34 million pledge to the institute by the Samsung Foundation, will allow the Pennsylvania biotech Inovio to expand development of its MERS vaccine, the only candidate against Middle East Respiratory Syndrome (MERS) now being testing in humans.
Co-developed in collaboration with Seoul-based GeneOne Life Science, Inovio’s DNA vaccine has been evaluated in mice, rhesus macaques and camels, inducing robust immune responses in all three species. Results showing 100% protection from a live virus challenge in a rhesus macaque non-human primate study supported moving the vaccine into the first Phase I human clinical trial of 75 healthy volunteers, being conducted in collaboration with the Walter Reed Army Institute of Research. With the trial fully enrolled and 75 subjects dosed, Inovio intends to report interim data in early 2017.
With success in the clinic, the company hopes to be in position to secure additional funding as well as work toward applying for emergency authorizations from regulators via the FDA’s “Animal Efficacy Rule.” Authorized by Congress in 2002 following the 9/11 attacks and concerns about bioterrorism, the “Animal Rule” provides a path to approval when human efficacy studies are not ethical or feasible. Through the pathway, companies may submit data from animal studies under certain circumstances to support their application.
5 December 2016
Major HIV vaccine trial debuts in South Africa
Seven years after an HIV vaccine trial conducted in Thailand, RV144, demonstrated modest protection against HIV infection, the first participant was enrolled last week in HVTN 702, the largest HIV vaccine trial to be conducted since RV144, and the largest ever in South Africa. HVTN 702 is a phase 3/2b study and the only HIV vaccine efficacy trial currently taking place worldwide.
HVTN 702 follows HVTN 100, which was a smaller phase 1/2 trial conducted in South Africa to see if a modified two-vaccine regimen used in RV144 was safe and could produce stronger immunological responses. Interim results from HVTN 100 presented in July at the 21st International AIDS Conference in Durban (AIDS 2016), provided the green light for a phase 3 efficacy trial, HVTN 702, based on the modified regimen.
The two-vaccine regimen used in RV144 has been updated and adapted for use in HVTN 702. Both vaccines, Sanofi Pasteur’s canarypox-based vaccine, ALVAC-HIV, and GSK’s gp120 protein subunit vaccine, have been modified to be specific to HIV subtype C, the predominant HIV subtype circulating in Southern Africa. Additional modifications have been made designed to boost immune responses and produce longer lasting protection.
HVTN 702 will enroll 5,400 HIV-negative study participants between the ages of 18 and 35 at 15 sites in South Africa. Sponsored by NIAID, the $130 million study is scheduled to run through 2020 and marks another milestone in the global effort to develop an HIV vaccine.
26 September 2016
Congress approves $1.1 billion funding bill to combat Zika
More than eight months after the White House first asked for it, Congress has finally agreed on funding to help fight the Zika virus and study its effects. The stopgap measure signed by President Obama last week provides $1.1 billion to use in continuing work on the development of a Zika vaccine, as well as studies of the effects on unborn babies, adults and children. It will also help states control the mosquitoes that spread the virus.
The $1.1 billion is just over half what federal health agencies say they need, and the approval squeaked through just two days before the end of the fiscal year on September 30.
The NIH and CDC had almost run out of fresh money to fight Zika, even after the administration had pulled $589 million to keep Zika research going from other programs, including $500 million meant to help prevent another Ebola outbreak. The two agencies had to plunder emergency preparedness, cancer, vaccine and HIV programs for more cash.
In the end, the legislation directs $394 million for mosquito control and $397 million for vaccine development and better tests to diagnose Zika infections. Of the $152 million that NIAID will receive from the new funding for Zika projects, nearly all will go to vaccine work.
2 September 2016
CEPI formally established
The Coalition for Epidemic Preparedness Innovations (CEPI) was formally established following a meeting of CEPI stakeholders at the Wellcome Trust in London on August 30. This announcement comes seven months after the World Economic Forum in Davos in January 2016 where the idea of a multinational partnership was born in a session devoted to vaccines and preparing for the next epidemic.
K. Vijay RagHavan, Secretary of the Indian Ministry of Science and Technology in Delhi, was elected CEPI chair, and Peter Piot, Director of the London School of Hygiene and Tropical Medicine, was elected CEPI vice-chair.
With this announcement, CEPI, which is as yet unfunded, is getting one step closer to the stage of preparing for a successful launch at the World Economic Forum in January 2017.
Congratulations to the FVR’s Stanley Plotkin, who co-chaired the science task force advising CEPI, and to the FVR’s Simon Wain-Hobson, who participated as a member of the science team.
"The formation of CEPI is the latest in a series of commendable initiatives post-Ebola to increase our preparedness ahead of the next pandemic. It is complementary to the proposed global vaccine development fund that is required to bridge the funding chasm that is impeding the development of vaccines for global diseases and infections that have been neglected for lack of a commercial market but which could save millions of lives.
We must not lose sight of the fact that we have a funding gap, and that resources will be needed on a massive scale to bridge this gap - both for pandemic preparedness and the endemic infections that continue unabated."
Prof. Simon Wain-Hobson, FVR Board Chair
Chief, Molecular Retrovirology
Institut Pasteur, Paris
16 May 2016
Industry leaders and policymakers express support for proposed fund in international forum organized by the Foundation and the National Academy of Medicine
"The stars are unusually aligned," said one senior vaccine industry expert. "We must seize this opportunity and not miss the occasion to act."
Industry leaders, government scientists and health officials, academicians and policymakers express support for the proposed global vaccine development fund and reform of the vaccine development process at a high-level, invitation-only international forum held May 16 at the National Academy of Sciences building in Washington DC.
Co-hosted and organized by the Foundation for Vaccine Research in partnership with the National Academy of Medicine, the forum drew 125 participants from the U.S. and around the world.
- Broad consensus that the status quo is unacceptable and that reform of the vaccine development process is needed
- Recognition that a persistent, identifiable, quantifiable financial gap is impeding the development of new vaccines
- Agreement that substantial resources are needed to bridge this gap, and that industry alone cannot be expected to assume the investment risk
- Acknowledgment that only governments have the resources on the scale required to bridge this gap and make this happen
- Increased support for exploring financial mechanisms to leverage funding and mobilize new assets, including the establishment of a pooled funding mechanism
- Recognition that the window of opportunity is fast closing
- Continue high-level consultations with stakeholders in the U.S. and globally
- Coordinate with other bilateral and multilateral initiatives
- Build political support to spur leadership, with special emphasis on U.S. government
- Conduct a series of high-level private briefings for members of U.S. Congress and other decision makers
- Prepare the groundwork for a major push by the next U.S. Administration
- G7 summit in Italy 2017
Read more and download program
Our forum poster features a flying fox bat (Pteropus hypomelanus) looking up while feeding in a mango tree on Tioman Island, Malaysia. These beautiful creatures, among the largest fruit bats, have a wing span of over 1 meter and can weigh over 1 kilo. They feed on fruit and nuts, and disperse seeds over vast distances. They also eat flowers and help pollinate numerous plants. As such, they are vital to the ecosystem. Unfortunately, they also carry Nipah virus. Encroachment on their habitat brings them into closer contact with humans, especially fruit growers and pig farmers. This has led to deadly outbreaks of Nipah virus infection in rural communities across Southeast Asia and beyond.
Nipah virus infection is a newly emerging zoonosis that can cause severe disease in both animals and humans. The virus’s natural hosts are fruit bats of the Pteropus genus, which are common throughout Southeast Asia. It was first identified during an outbreak of disease that took place in Kampung Sungai Nipah, Malaysia in 1998 – hence the name “Nipah” virus. On this occasion, pigs were the intermediate hosts. However, in subsequent outbreaks, there were no intermediate hosts. More outbreaks of Nipah virus have occurred since 1998, all within Bangladesh and neighboring parts of India.
In Bangladesh in 2004, humans became infected with Nipah virus as a result of consuming date palm sap that had been contaminated by infected fruit bats. Human-to-human transmission has also been documented, including in a hospital setting in India. Nipah virus infection in humans has a wide range of clinical presentations, from asymptomatic infection to acute respiratory syndrome and encephalitis. While variable, the overall case fatality rate is around 75%, which is huge.
There is no vaccine against Nipah virus infection for either humans or animals but several experimental vaccines are in development. For the moment, the primary treatment for human cases is intensive supportive care. The WHO has called for prioritizing and stepping-up research that would lead to the licensure of a safe and effective Nipah virus vaccine.
Photo: Stéphane Bidouze
About the event
This international forum was held under the Chatham House Rule. The purpose was to build on the momentum generated by Ebola and Zika to focus attention on the need for comprehensive reform of the vaccine development process and how to accelerate the availability of new vaccines in advance of epidemics.
Topics for discussion included advances in science and technology, global research priorities, resource needs, financial gaps, resource allocation, mobilization of new assets, the merits and feasibility of different financing mechanisms that have been proposed to bridge these gaps, and the exploration of opportunities for greater collaboration and partnerships globally to maximize synergies and achieve mutual goals.
The Foundation for Vaccine Research
The National Academy of Medicine
Event chairs and co-chairs
Victor J. Dzau
Adel A.F. Mahmoud
Salim Abdool Karim
Speakers (in order of presentation)
Event format and target audience
This event was designed for decision makers, policy makers and other leaders, bringing together 125 scientists, industry leaders, funders, public health officials and other experts from the U.S. and globally, with knowledge of the challenges facing vaccine developers.
It was hoped that a set of recommendations would emerge from the meeting that will help advance the global discussions currently underway on how to accelerate the development and availability of new vaccines. In addition, it was hoped that the meeting would generate increased support for exploring new mechanisms to leverage financing and mobilize new assets to speed vaccine development.
Date and venue
Monday 16 May: Main event - all-day meeting from 8:00 am to 6:00 pm in the Lecture Room at the National Academy of Sciences building at 2101 Constitution Avenue NW, in Washington, DC.
Mix of topics
50% science, 50% policy. The agenda was designed to allow ample time for discussion at the end of each session, and a full hour for discussion in the last session of the day.
Event sponsors and strategic partners
The Bill & Melinda Gates Foundation
The Wellcome Trust
23 July 2015
Call for establishing a global vaccine development fund published in the New England Journal of Medicine.
Plotkin SA, Mahmoud AAF, Farrar J. Establishing a global vaccine development fund. N Engl J Med. 2015 Jul 23;373(4):297-300
Vaccine-Preventable Diseases and Infections and Targets Currently Uncontrolled by Vaccination. Updated August 21, 2015.*
Diseases and infections with commonly used vaccines
- Haemophilus influenzae type b
- Hepatitis type A
- Hepatitis type B
- Human papillomavirus (HPV)
- Influenza types A and B (seasonal)
- Japanese encephalitis
- Pertussis (whooping cough)
- Tickborne encephalitis
- Varicella (chickenpox)
- Yellow fever
Diseases and infections with limited-use vaccines
- Adenovirus types 4 and 7
Diseases and infections with no vaccines or only partially effective vaccines
- Chlamydia Moraxella
- Clostridium difficile
- Ebola and viral hemorrhagic fevers
- Enterovirus including EV71, EV68, CA16
- Epstein-Barr virus
- Escherichia coli
- Haemophilus influenzae, nontypable
- Helminths (numerous)
- Hendra virus
- Hepatitis type C
- Hepatitis type E
- Herpesvirus type 6
- Herpes simplex
- Influenza, universal
- Influenza, avian types H5 and H7
- Lyme disease
- Moraxella (for otitis)
- Neisseria gonorrhoeae
- Nipah virus
- Nosocomial bacteria
- Salmonella paratyphi
- Strep Group A
- Strep Group B
- West Nile virus
* Updated information is from the Foundation for Vaccine Research. Nipah and Hendra viruses were unintentionally omitted in the list published in NEJM. MERS denotes Middle East Respiratory Syndrome, RSV Respiratory Syncytial Virus, and SARS Severe Acute Respiratory Syndrome. Vaccines for some of the targets indicated above are in advanced development, but most are not.
28 January 2016
Zika virus added to list of priority targets for proposed fund
The spread of Zika virus in the Americas has become a major source of concern since its pathogenicity has become more clear. Particularly worrisome is the alarming jump in the reported number of cases of infant microcephaly in Brazil. Adding Zika virus and Paratyphoid A (Salmonella enterica) brings the list of priority targets to 17, in close alignment with WHO's list of dangerous pathogens put out on 12 December 2015.
Learn more about Zika virus
The Zika virus is a flavivirus, part of the same family as yellow fever, West Nile, chikungunya and dengue viruses. Like them, it is transmitted to humans via the bite of an infected Aedes sp. mosquito. But unlike some of those viruses, there is no vaccine to prevent Zika or medicine to treat the infection. Zika is commanding worldwide attention because of an alarming, suspected but not proven connection between infection with the virus and microcephaly, a neurological complication that results in babies being born with abnormally small heads. This causes severe developmental issues and sometimes death. Since November 2015, Brazil has reported 4,180 cases of microcephaly in babies born to women who were infected with Zika during their pregnancies, compared to only 146 cases in 2014. Authorities have not been able to confirm that all 4,180 cases are attributable to infection with the virus. So far, 51 babies have died. Until recently, the virus was considered relatively harmless. In 80% of cases, it causes no symptoms and people are unaware they have been infected. In 20% of cases, it causes Zika fever, a mild disease with symptoms including rash, joint pain and conjunctivitis. The Zika virus was first identified in Uganda in 1947. It was not until 2015 that a previously unknown connection between Zika infection in pregnant women and microcephaly in newborns was reported.
17 priority targets (updated January 28)
Same criteria as before (see note below). List modified to provide more detail on prioritization based on the latest information.
- Ebola hemorrhagic fever virus
- Lassa hemorrhagic fever virus
- Marburg hemorrhagic fever virus
- MERS coronavirus
- SARS coronavirus
- Crimean-Congo hemorrhagic fever virus
- Chikungunya virus
- Nipah virus
- Hepatitis E virus
- Zika virus
- Enterovirus 71
- Enterovirus 68
- Coxsackievirus 16
- Paratyphoid A (Salmonella enterica)
- West Nile virus
- Rift Valley fever virus
- Plague (Yersinia pestis)
The criteria used for developing this updated list are unchanged. They include: case fatality rate; transmissibility and capacity for human-to-human transmission; frequency of outbreaks; geographical spread; existence of other interventions, investment, and development stage globally; and scientific feasibility of candidates.
Source: Working group
20 January 2016
Vaccine development fund to be discussed at the World Economic Forum in Davos.
The proposed global vaccine development fund called for in The New England Journal of Medicine will be discussed at a high-level, 90-minute closed session at the Davos summit on 21 January. Moderated by Dr. Peter Piot, the session will be attended by 30 senior decision makers from governments, industry, foundations, WHO, MSF, and other stakeholders. The purpose of the meeting is to forge a broad consensus on the way forward in the development of the fund.
12 January 2016
Leading vaccinologist endorses proposed fund
“In 1955, twenty-seven companies made vaccines. By 1980, due to drop out and merger, 18 vaccine makers remained. Today, only 4 major pharmaceutical companies focus on vaccines. This dramatic decline isn't because infectious diseases are now a thing of the past. Quite the opposite. Recent outbreaks of viral diseases like MERS-CoV, SARS, Ebola, West Nile, and chikungunya show that vaccines are needed now more than ever before. The problem is that the business model is geared to products with only a large market potential. Something needs to be done. Perhaps the single best solution would be the creation of a global vaccine development fund that would promote the development of vaccines that currently have fallen through the cracks. Without such a program, the continued erosion in vaccine research and development is inevitable.”
Paul Offit MD
Maurice R Hilleman Professor of Vaccinology
Co-inventor of the rotavirus vaccine
and Professor of Pediatrics
The Children's Hospital of Philadelphia
1 January 2016
Scientifically feasible vaccines against major diseases are stalled for lack of funds, says Science.
In a feature article entitled “Unfilled Vials,” the journal Science names 10 top candidate vaccines that need a boost. “Vaccines that appear scientifically feasible often move through development slowly because they have little commercial potential and thus have trouble attracting serious investments,” writes Jon Cohen, senior Science reporter who covers vaccines. “Just such a situation held back R&D on Ebola vaccines, one of which quickly proved its worth in a real-world trial held in Guinea last year. In the wake of that success, a growing number of researchers and public health advocates are lobbying to find new money and strategies to develop vaccines that could thwart both outbreak diseases like chikungunya and Marburg to endemic afflictions like paratyphoid fever and schistosomiasis. In the past few weeks, the WHO and the nonprofit Foundation for Vaccine Research have taken a stab at identifying what those vaccines are, and they’ve zeroed in on the exact same targets.”
Cohen went on to describe in some detail the proposed $2 billion global vaccine development fund called for in The New England Journal of Medicine last July, noting that it is on the agenda to be discussed at the World Economic Forum in Davos, Switzerland, on 21 January.
9 December 2015
Priority targets provisionally identified for proposed fund
Fifteen infections have been provisionally identified as priority targets for the fund. Criteria used include: case fatality rate; transmissibility and capacity for human-to-human transmission; frequency of outbreaks; geographical spread; existence of other interventions, investment, and development stage globally; and scientific feasibility of candidates.
15 priority targets
- Hemorrhagic fever viruses (Ebola,* Marburg, Lassa)
- SARS and MERS coronaviruses
- Chikungunya virus
- West Nile virus
- Nipah virus
- Hepatitis E virus
- Enteroviruses (EV68, EV71 and CA16)
- Crimean-Congo hemorrhagic fever
- Rift Valley fever
- Plague (Yersinia pestis)
*To support licensure of existing candidates against Ebola Zaire species and the development of less advanced, multivalent, next-generation vaccines protective against Zaire, Bundibugyo and Sudan Ebola viruses.
Note: The fund’s purpose is to accelerate vaccine development globally for new and emerging infections, as well as neglected diseases and infections endemic in developing countries for which there is low market potential. Considerable resources are already being employed developing vaccines for pandemic influenza, Respiratory Syncytial Virus (RSV), HIV, Tuberculosis, malaria and Dengue, all of which are top priorities but outside the scope of the proposed fund.
Source: Working group
24 November 2015
World needs to create a fund to help pay for vaccine development, say experts in The Guardian.
“There are many diseases, like Ebola, for which no vaccine has yet been developed and this is largely because there is very little incentive for companies or public institutions to undertake research and development. To overcome this challenge, the world needs to create a fund to help pay for the development and distribution of vaccines for this and many other emerging epidemics and infectious diseases.”
Director, London School of Hygiene & Tropical Medicine
Co-discoverer of the Ebola virus in 1976 in Zaire (now Democratic Republic of the Congo)
Chief scientific officer and worldwide chairman of Johnson & Johnson Pharmaceuticals group
22 November 2015
Harvard-LSHTM panel recommends a global facility to finance, accelerate, and prioritise R&D.
An independent panel of 19 experts convened by the Harvard Global Health Institute and the London School of Hygiene & Tropical Medicine has issued a hard-hitting analysis of the global response to the 2014 Ebola outbreak in West Africa, published in The Lancet.
Among ten essential reforms, the panel recommends establishing a global facility to finance, accelerate, and prioritize research and development, citing the New England Journal of Medicine paper calling for establishing a global vaccine development fund.
Members of the Panel
Dr Suerie Moon, Harvard Global Health Institute/Harvard School of Public Health/Harvard Kennedy School (Study Director)
- Professor Peter Piot, London School of Hygiene & Tropical Medicine (Chair)
- Dr Ashish Jha, Harvard Global Health Institute/Harvard School of Public Health (Co-chair)
- Dr Muhammad Pate,
Duke University (Co-chair)
- Dr Devi Sridhar,
Edinburgh Medical School (Co-chair)
- Dr Chelsea Clinton,
Bill, Hillary & Chelsea Clinton Foundation
- Ms Sophie Delaunay,
Médecins Sans Frontières
- Ms Valnora Edwin,
Campaign for Good Governance
- Dr Mosoka Fallah,
Action Contre La Faim International (ACF)
- Mr David Fidler,
Indiana University Maurer School of Law
- Dr Eric Goosby,
University of California, San Francisco
- Ms Laurie Garrett,
Council on Foreign Relations
- Dr Larry Gostin,
- Dr David Heymann,
- Dr Kelley Lee,
Simon Fraser University
- Dr Gabriel Leung,
The University of Hong Kong
- Dr Steve Morrison,
Center for Strategic and International Studies
- Dr Jorge Saavedra,
AIDS Healthcare Foundation
- Dr Marcel Tanner,
Swiss Tropical & Public Health Institute
Recommendation 7: Establish a global facility to finance, accelerate, and prioritise research and development
The UN Secretary General and WHO Director-General should convene in 2016 a high-level summit of public, private and not-for-profit research funders to establish a global financing facility for research and development for health technologies relevant for major disease outbreaks. The facility would support manufacturing, research and development for drugs, vaccines, diagnostics and other non-pharmaceutical supplies (such as personal protective equipment) where the commercial market does not offer appropriate incentives. For known pathogens, the facility could invest in bringing candidate drugs, vaccines, technology platforms, and other relevant products through proof of concept, phase 1 and phase 2 testing in humans, so that they are ready for wider testing, manufacturing, and distribution when an outbreak strikes. During an outbreak the fund would rapidly mobilise financing for priority research and development projects, such as diagnostics for novel pathogens.
The establishment of a similar fund for diseases affecting developing countries was a central recommendation of the 2012 report of the WHO Consultative Expert Working Group on research and development.1 As a result, a pooled international fund was created to support “demonstration projects” that test new research and development business models, such as open knowledge innovation and de-linkage of research and development financing from end product prices. With a management structure already established, the demonstration projects offer an important option for pursuing research and development for Ebola or other diseases.
The global financing facility should be a lean, efficient entity that mobilises and strategically deploys resources. It would not be a monolithic entity nor the sole funder for epidemic-related research and development because some pluralism and competition among funders is desirable. Nevertheless, a global facility would offer the advantage of facilitating coordination among different research funders through a common framework, strengthening networks between researchers, establishing processes for priority setting, and reducing transaction costs for both grantees and smaller donors.2,3 It could also require information sharing among researchers as a condition of funding, thereby giving teeth to the data-sharing framework (recommendation 6). Intellectual property or any other asset resulting from these investments should be managed as a public good to facilitate follow-on innovation, open knowledge sharing, access to technology and a fair public return on investment. Support for a global research and development financing mechanism now seems to be growing, as shown in calls for a $2 billion global fund for vaccine development for pandemics,2 a $2 billion global fund for antimicrobial resistance,4 and a $2-3 billion global fund that would cover emerging infectious diseases, neglected diseases and antimicrobial resistance.5
- 1 WHO Consultative Expert Working Group on research and development: Research and development to meet health needs in developing countries: Strengthening global financing and coordination. 2012. http://www.who.int/phi/CEWG_Report_5_April_2012.pdf (accessed May 29, 2015).
- 2 Plotkin SA, Mahmoud AA, Farrar J. Establishing a Global Vaccine-Development Fund. N Engl J Med. 2015; 373:297-300.
- 3 Moon S. Demonstration financing: considerations for the new international fund for R&D. 2014. http://www.dndi.org/images/stories/advocacy/pilot-pooled-international-fund_web.pdf (accessed July 25, 2015).
- 4 O’Neill J. Securing new drugs for future generations: the pipeline of antibiotics. 2015. http://amr-review.org/sites/default/files/SECURING NEW DRUGS FOR FUTURE GENERATIONS FINAL WEB_0.pdf (accessed May 29, 2015).
19 November 2015
World-renowned Institut Pasteur is first to endorse the proposed fund
“The Institut Pasteur has been at the forefront of the fight against many epidemics over the past century, most recently against Ebola. Research in vaccinology is at the heart of our legacy and we are significantly reinforcing our efforts in this area. The Institut Pasteur is pleased to support your most valuable efforts to set up a global vaccine development fund. The initiative you have launched is a most important progress for the control of infectious diseases; clearly, this is what should be implemented to meet with the next epidemics, worldwide.”
Professor Christian Bréchot
President, Institut Pasteur
1 November 2015
Foundation hosts second planning meeting of the core group in Dublin
The FVR’s Board Chair Simon Wain-Hobson, Institut Pasteur, and FVR Director Adel Mahmoud, Princeton University, host a planning meeting of the core group driving the proposed vaccine development fund at the Westin Dublin Hotel. Held on the eve of the Princeton-Fung Global Forum 2015 on lessons learned from the Ebola crisis, this highly-productive meeting marked another milestone in the fund’s development with agreement on the need to set up an interim secretariat.
The Dublin meeting follows an inaugural meeting of the core group in a retreat-like setting hosted by Dr. Mahmoud at his home in Princeton on September 12-13. The group has since expanded from five to seven members.
Global Vaccine Development Fund Working Group
- Jeremy Farrar MD PhD
- Tore Godal MD
- Peter Hale
- Adel AF Mahmoud MD PhD
- Peter Piot MD PhD
- Stanley A Plotkin MD
- Simon Wain-Hobson DPhil
Contact: Peter Hale
c/o The Foundation for Vaccine Research
Office +1 202 587 2754
Mobile +1 202 297 7458
29-30 October 2015
Support for proposed fund grows in Oslo consultation
The FVR’s founder and executive director Peter Hale gives a talk on the proposed vaccine development fund in Oslo at a high-level consultation organized by the WHO and the Norwegian Institute of Public Health on financing for R&D preparedness. The outcome of the consultation will inform the development of a blueprint for accelerating R&D in future epidemics or public health emergencies.
21-22 September 2015
Proposed fund makes its debut at World Bank-WHO meeting in Washington
The FVR’s Stanley Plotkin makes the case for the proposed global vaccine development fund in a special session of the World Bank Group-WHO stakeholders meeting on pandemic financing at the World Bank in Washington.
21 August 2015
Support builds for reform of vaccine development through proposed fund.
Global Dispatches Podcast
Interview with Dr. Jeremy Farrar, Professor of Tropical Medicine and Director of the Wellcome Trust, in which he discusses the implications of the recent Ebola vaccine trial and how the creation of a global vaccine development fund will spur the development and deployment of vaccines to counter fast emerging epidemics. (12:00)