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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
"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
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 just over 60% of the 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.
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 21.
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
15 November 2015
The Foundation will be moving over the Thanksgiving weekend from 1425 K Street NW into sparkling new offices in the Paramount Building at 1775 Eye Street NW in Washington, DC. Please note our new address. Our phone and fax numbers stay the same.
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)