Breakthroughs Blog: Vaccines

There is a safe, affordable, single-dose vaccine that protects against yellow fever for 99 percent of those vaccinated, yet a recent outbreak of the disease has resulted in nearly 2,000 cases and killed 258 in Angola. Yellow fever is endemic in 44 countries, including Angola, and the global demand for the vaccine surpasses availability by 42 percent. Additionally, the cost of the vaccine has increased 30 percent annually. The vaccine is currently produced by four manufacturers, and its production is complicated, requiring embryos in chicken eggs. A vaccine with an inactivated version of the virus, which would be much easier to manufacture, has successfully completed phase 1 clinical trials, however, it has not yet been commercialized. As the World Health Organization is leading negotiations to divert yellow fever vaccines from routine immunization programs to Angola, the existing vaccine could also be delivered in smaller quantities to more people: just one-fifth of the standard dose has proven to be effective against the virus. A team of American and German scientists have demonstrated that an injection with potent anti-HIV antibodies can protect against the virus in monkeys for nearly six months. The researchers used four different antibodies that have proven to be effective against various HIV strains and administered one type each to four different groups of monkeys. The monkeys were then exposed to the virus on a weekly basis. On average, the monkeys were protected for 12 to 14 weeks, although some were protected for up to 23 weeks. Previous studies have shown that antibodies can provide short-term protection against HIV in monkeys, however, in most studies, the monkeys were exposed to the virus in one high-dose shot. In reality, most infections in humans develop gradually as a result of repeated, low-dose exposures, and thus, this study sought to emulate standard human transmission. Currently, the first-ever clinical trial of a single antibody is being tested in individuals at high-risk for HIV infection, however, it’s expected that a cocktail of these potent antibodies would be even more effective at preventing infection.  New research out of Florida Gulf Coast University indicates that previous infection with dengue virus could exacerbate symptoms from the Zika virus. This phenomenon—antibody-dependent enhancement, in which the presence of protective antibodies against one disease increases vulnerability to another—has been reported among different strains of dengue virus. The team at Florida Gulf Coast University confirmed that in cell cultures, the presence of antibodies against dengue intensified Zika infection, however the research also suggests that a single vaccine candidate could be effective against both diseases. These findings, coupled with the shared Aedes aegypti mosquito vector, indicate that the spread of Zika in dengue-endemic regions could be more virulent than expected. 

This post is part of the #MarketsMatter expert blog series. Read the full series here. The size, strength, and stability of markets dictate how health product developers set priorities and fund research and development (R&D); a 1 percent increase in the potential market size for a drug category leads to a 6 percent increase in the number of medicines introduced in the US market.[i] However, relying on market forces alone to drive health R&D leads to staggering disparities in funding and real-world impact. Today, only 1 to 2 percent of all global investment in health R&D targets neglected diseases, which kill more than 6 million people each year and disproportionately affect low- and middle-income countries (LMICs).US Navy Lt. Kimberly Edgel, left, and Christian Baldeviano examine a positive malaria blood smear at Naval Medical Research Unit (NAMRU) 6 in Callao, Peru. When existing market forces alone fall short in ensuring availability of and access to lifesaving health tools, a range of interventions are needed to alter the market and ultimately change the behavior of its actors. Incentives and innovative financing mechanisms are interventions that have proven effective in accelerating R&D and delivering lifesaving vaccines, drugs, diagnostics, and other health tools to those who need them most. Incentives such as advance market commitments (AMCs), volume guarantees, milestone prizes, and priority review vouchers reward developers who conduct neglected disease R&D or guarantee a market for a health product, ensuring that developers are able to recoup the costs of R&D. Innovative financing mechanisms, including mix-method financing, cross-sector partnerships, pooled funding, and competitions directly subsidize and consequently catalyze R&D. These platforms and partnerships are already accelerating R&D and promoting access to new innovations. AMCs—agreements by procurers to purchase a specified quantity of a new product at a predetermined price, effectively securing a market for product developers—have moved from innovative idea to reality over the past decade. In 2007, Gavi, the Vaccine Alliance launched an AMC for pneumococcal vaccines, raising US$1.5 billion from six public and philanthropic donors to purchase a future vaccine. While there were already two late-stage candidates in the pipeline that met the AMC’s criteria, the commitment created competition and encouraged GlaxoSmithKline (GSK) and Pfizer to adapt the vaccine candidates for low-resource settings. The AMC also stimulated demand; the vaccine has been introduced in more than 50 LMICs, and both GSK and Pfizer scaled up manufacturing to meet the demand, reporting that these decisions were influenced by the existence of the AMC. Earlier this year, Gavi initiated a similar agreement, signing an advance purchase commitment with Merck, providing $5 million toward the development of an Ebola vaccine. Merck guaranteed that the product would be submitted for licensure by the end of 2017, and 300,000 doses would be made available by May 2016 for use in either a future outbreak or clinical trial. Not only has Ebola historically affected LMICs, but the disease typically emerges in short-term outbreaks, and thus, the market is limited and unstable. This agreement will ensure that a stockpile of vaccines are ready to be deployed during the next outbreak and signals to vaccine developers and manufacturers that cross-sector partnerships can offer a market for emerging and reemerging infectious diseases. While incentive mechanisms can expedite product development and access to new health tools by creating market demand and new financial incentives, innovative financing mechanisms that directly fund R&D remain critical and have played a tremendous role in bolstering the neglected disease pipeline. The pipeline has grown from 365 products in 2012 to 485 tools today, three-fourths of which are being developed by public-private partnerships, including product development partnerships, which facilitate collaboration across the public, private, and philanthropic sectors, bringing in new resources and diverse expertise. Other innovative financing mechanisms include pooled funds, such as the Global Health Innovative Technology (GHIT) Fund, which is financed by the Japanese government, seven Japanese pharmaceutical companies, and the Bill & Melinda Gates Foundation. The GHIT Fund has brought new investors and resources to the table and is currently supporting nearly 50 drug, vaccine, and diagnostic candidates. Alternately, Grand Challenge programs offer a platform for open innovation, identifying and financing promising ideas to address health and development challenges. Through its Grand Challenges series, the US Agency for International Development has elicited 7,400 ideas and has supported 224 of them, leveraging $125 million in new funding to match the agency’s investment of $76 million. Markets for neglected disease products are often perceived as insufficient to warrant investments in R&D, and thus, we can’t rely on existing market forces alone to determine R&D funding and priorities. An enabling policy environment, cross-sector partnerships, and innovative financing mechanisms have a critical role to play in galvanizing greater industry engagement and addressing the market failures that inhibit neglected diseases R&D.The Global Health Technologies Coalition (GHTC) works to save and improve lives by encouraging the research and development of essential health technologies. We are a coalition of more than 25 nonprofit organizations advancing policies to accelerate the creation of new drugs, vaccines, diagnostics, and other health tools that bring healthy lives within reach for all people. GHTC is housed at PATH and funded in part by the Bill & Melinda Gates Foundation. Learn more at www.ghtcoalition.org. [i] According to the authors of this study, the correlation between market size and new drugs entering the market likely applies beyond the US market, but this data is not readily available. However, the US market has a disproportionate impact on R&D funding and priorities, as it constitutes an estimated 40 percent of the global market. For more information, see the study, published in The Quarterly Journal of Economics, here.

A vaccine candidate against Rift Valley Fever appears to be safe and effective for livestock and has the potential for use in humans. Rift Valley Fever—which was recently identified by the World Health Organization (WHO) as a leading culprit for the next major pandemic—is often asymptomatic, or manifests with nonspecific symptoms that are easily confused with malaria. However, severe cases can involve vision impairment, brain swelling (encephalitis), hemorrhagic fever, or death. The disease is caused by a virus and transmitted to humans through mosquito bites or contact with infected animal tissue. While there is a veterinary vaccine against Rift Valley Fever used throughout Africa, it does not provide complete protection from the disease and can induce abortion. The vaccine uses a virus that causes cold-like symptoms in chimpanzees, an approach that is generally safe for humans. The candidate will next be tested in animal trials across East Africa, which will be followed by human clinical trials in the region. Middle East Respiratory Syndrome Coronavirus (Photo: National Institute of Allergy and Infectious Diseases (NIAID)) Last week, the Walter Reed Army Institute of Research (WRAIR) initiated the first-ever human clinical trials for a vaccine against the Middle East Respiratory Syndrome (MERS). The DNA-based vaccine was developed by Inovio Pharmaceuticals and GeneOne Life Sciences Inc., and the two companies are also partnering to develop vaccines against Ebola and Zika. MERS is endemic in the Middle East, however, an outbreak last spring in South Korea resulted in 186 cases and 36 deaths. The United States currently has 35,000 and 27,000 troops in the Middle East and South Korea, respectively, and as 40 percent of MERS cases are fatal, “low prevalence doesn’t mean low risk” according to Dr. Kayvon Modjarrad, associate director of the Emerging Infectious Disease Research Program at WRAIR. Meanwhile, a team of researchers at Erasmus Medical Center in Rotterdam is testing a MERS vaccine in camels in Saudi Arabia, where 12 percent of camels are infected at any time and camel-to-human transmission is a significant driver of new cases. Inovio Pharmaceuticals and GeneOne Life Sciences Inc. are also conducting animal studies of their vaccine against Zika, and announced last week that the candidate successfully prompted an immune response in mice, including the development of antibodies against Zika. The partners will next test the candidate in primates and begin Phase 1 human clinical trials by the end of the year. However, vaccine candidates developed by Bharat Biotech in India and the US National Institutes of Health (NIH) are farthest along, according to the WHO. Bharat Biotech will launch animal studies within the next few weeks and the NIH plans to start human clinical trials of at least one of their two vaccine candidates by the end of this summer. As more than 15 groups across government, industry, and academia have joined the hunt for a Zika vaccine, US Congressman Curt Clawson (R-FL) has introduced legislation to further incentivize Zika research and development (R&D), providing companies a 10 percent tax credit for any Zika vaccine R&D costs. The legislation was accompanied by two additional bills, the first of which would reauthorize a program—at US$200 million per year for five years—to support states with mosquito control and prevention. Clawson’s third piece of Zika-related legislation would allow supplemental funding for the Ebola response to be used for Zika, however, leaders at the NIH and US Centers for Disease Control have stated that the remaining Ebola funding has already been reprogrammed and that the agencies have had to take funding away from other programs to kickstart the Zika response.

In this guest post Tom Harmon, senior policy analyst at the International AIDS Vaccine Initiative (IAVI), highlights a new analysis exploring the critical role of a vaccine in ending AIDS. Photo credit: IAVI When we talk about ending AIDS, what do we mean? The last dozen years have brought tremendous strides in reducing new HIV infections in low- and middle-income countries (LMICs), expanding lifesaving treatment to almost 16 million people living with HIV, and implementing programs to address the epidemic in populations at especially high risk, including women and girls. But we must continue to push for progress in treatment and prevention. The 2 million new infections in 2014 remain far too high, and almost 60 percent of people needing treatment are not getting it. So, when we talk about conclusively and durably ending AIDS and ensuring that it does not bounce back, our experience with other infectious diseases shows that a preventive vaccine will be necessary. The global effort to develop an AIDS vaccine has also recently experienced significant successes and steps forward. For example, we’ve never before seen such a diversity of approaches and partners, with follow-on trials based on the first candidate to show modest efficacy slated to begin later this year in South Africa, exciting new insights toward generating protective antibodies against HIV, and promising approaches toward inducing cellular immune responses that could control HIV infection. Still, there are more far-reaching questions we’re asked today by policymakers, advocates, communities, and even researchers themselves: What would the global response look like if an AIDS vaccine was available? How effective would it need to be? Would it be cost-effective and affordable? A new article, published in PLoS ONE aims to answer some of these crucial questions. The result of a collaboration between IAVI, Avenir Health, and AVAC that builds on work by UNAIDS, this model specifically explores a vaccine’s potential value in terms of preventing HIV infections in LMICs. We analyzed a vaccine’s potential impact depending on how well the world can achieve ambitious HIV and AIDS program objectives, how effectively it can prevent HIV infection, and how it can add to a response that also includes pre-exposure prophylaxis and treatment as prevention. We also looked at cost scenarios to see how a vaccine would stand up to cost-effectiveness criteria used by the World Health Organization to guide the introduction of new health technologies. Despite the potential for today’s tools to have a substantial impact on the epidemic, our results show that a vaccine is a critical piece to ending AIDS. Under our base scenario, a vaccine of 70 percent efficacy with strong uptake would reduce HIV infections in LMICs by 44 percent in its first 10 years and by 65 percent in 25 years, ultimately averting tens of millions of infections and saving millions of lives. Reduction of new annual HIV infections with PrEP, TasP and vaccination added individually and in combination to the Full Scale-up of IFE between 2015 and 2070. A vaccine would be impactful and cost-effective even at lower efficacy levels and costs far higher than many of today’s vaccines. Increasing a vaccine’s efficacy, ensuring it protects for a longer period of time, reducing the number of doses, lowering the cost of a dose, and more effectively rolling it out are all factors that would increase a vaccine’s impact and its value. Such a vaccine could cut the number of people needing treatment in half by the year 2070, and eventually reduce the total cost of fighting AIDS in LMICs even when the additional cost of implementing the vaccination program is included. While these data provide a powerful illustration of a vaccine’s potential value, we acknowledge and welcome discussions of its intrinsic limitations, which reflect the areas the AIDS vaccine field and future program implementers will need to tackle as we research, develop, and ultimately deliver a vaccine to the people who need it most. Such an analysis helps explore the parameters that determine the medical and economic impact and value of a future AIDS vaccine as part of the comprehensive HIV and AIDS response. This data can be a useful guide for research portfolio decisions as new candidates move closer to efficacy trials. In many ways these projections are as much a vaccine development and delivery “to-do list” as they are a crystal ball for what the future holds. A few weeks ago, the US Centers for Disease Control and Prevention organized a Grand Rounds presentation on how models are used to guide pandemic responses. This interesting panel was closed by Dr. Richard Hatchett, chief medical officer and deputy director for strategic sciences at the US Biomedical Advanced Research and Development Authority, who cited modeler Steven Bankes’ use of campfires as an analogy for predictive models, in that their value goes beyond their primary deliverable (be it light, heat, or data), as they just as importantly provide a “gathering place” for discussion between stakeholders. Our new model can perform just such a dual function, adding valuable context for a vaccine’s future role in ending the AIDS epidemic which has ravaged so many communities, while stimulating conversations and new questions on what we need to do in the real world to turn theory to impact.