Breakthroughs Blog: Vaccines

Margaret McGlynn is the president and CEO of the International AIDS Vaccine Initiative (IAVI). In this guest post to mark HIV Vaccine Awareness Day, she writes about the potential impact of a safe and effective HIV vaccine around the world. The post originally appeared on the US Agency for International Development’s (USAID) Impact blog. Throughout my career, I have witnessed the tremendous power of vaccines to prevent sickness and save lives—delivering incredible victories for humanity against diseases such as polio, smallpox, and measles. These vaccines would not have been possible without the inspiration, persistence, and courage of researchers, volunteers, and health workers around the world. And so today, on HIV Vaccine Awareness Day, I join countless others around the world in reflecting on what it would mean to see AIDS consigned to a list of former pandemics. To achieve that goal, it is essential that we enlist the participation of researchers around the world in the design and development of HIV vaccines. Young researchers such as Gladys Njeri Macharia in Kenya—who has dedicated her career to exploring immune responses to HIV—will play an especially important role in that effort. And one day, critical scientific questions addressed by this research might help lead to an effective vaccine. Thanks to a USAID-supported program, Gladys Njeri Macharia is studying how rare individuals might be blocking HIV infection. Photo credit: IAVI New modeling data available today from IAVI and the Futures Institute, with support from USAID, illustrates how a safe, preventive HIV vaccine that is accessible and affordable can help us end the AIDS pandemic. This information is available in a series of publications and an interactive web tool. The potential impact of a vaccine is striking. Because HIV is so extraordinarily resistant to the immune response, it is highly unlikely that any single vaccine will be able to prevent infection by all variants of the virus. Still, our modeling shows that if an AIDS vaccine that is only 50 percent effective is introduced in 2020 to 30 percent of the population in low- and middle-income countries, 5.2 million new HIV infections could be averted over the first decade. Higher efficacy and more coverage would have an even greater impact on the pandemic. The world must continue to scale up and improve the response to HIV by using powerful prevention tools that are currently at our disposal. These include condoms, treatment, and voluntary medical male circumcision. Our new models show that a vaccine can build on these existing tools and take us down the last mile to the end of the AIDS pandemic. A 50 percent effective vaccine combined with greater use of current HIV-prevention tools could prevent nearly 20 million new HIV infections by 2030—20 million people that would not need to face the physical, emotional, and social hardships caused by the disease and could avoid lifelong, daily antiretroviral treatment to stave off AIDS-related illness or death. This HIV Vaccine Awareness Day, IAVI and our partners remember those we have lost to AIDS, gain inspiration from those living with and combating the disease today, and look forward to building on the incredible momentum of recent discoveries and study results to deliver on the tremendous potential of an AIDS vaccine. To access IAVI and the Futures Institute’s impact modeling publications and interactive modeling tool, visit www.iavi.org/

Michel Zaffran is the coordinator for the Expanded Programme on Immunization at the World Health Organization (WHO). He is also the director of Project Optimize at PATH. In this guest post, Zaffran writes about how the Bill & Melinda Gates Foundation is seeking new ideas for immunization systems and vaccine product characteristics. As one of the most cost-effective health interventions, new lifesaving vaccines bring great promise to communities around the world. However, these new vaccines often present challenges to the immunization supply systems of low- and middle-income countries. Some new vaccines can occupy more space, may be more complex to prepare for administration, and may have temperature requirements that are not suited to the challenging environment of low- and middle-income countries. The Bill & Melinda Gates Foundation’s Grand Challenges Explorations grants program has launched a new call seeking ideas to improve immunization supply systems, including vaccine product characteristics that could have implications for research and development. For example: Tools to enable countries, donors, and procurement agencies to assess the systems costs and benefits of vaccine product presentations and formulations, rather than product price alone, in order to inform their vaccine purchase decisions and optimize their relevance to immunization strategies. Low-cost vial-level temperature indicators that display both cumulative and peak exposures to heat. Non-formulation means to prevent vaccines from freezing and/or to guarantee the sterility of opened multi-dose vials during storage and use. Any other innovation relevant to vaccine characteristics that do not necessarily involve preclinical or clinical research or improving vaccine stability or formulation. Anyone with a good idea is eligible to submit a two-page proposal, including public health specialists, researchers, entrepreneurs, engineers, or students working in nongovernmental organizations, ministries of health, universities, or companies. The program offers $100,000 grants, and successful projects may be eligible for additional funding up to $1 million. The submission deadline is May 15, 2012. This call for proposals builds on work facilitated by Project Optimize—a collaboration between PATH and the WHO—to develop a common vision for the future of immunization supply systems and logistics. More information Grand Challenges Explorations call for proposals Grand Challenges Explorations program Project Optimize on the PATH and WHO websites.

In this guest post, Dick Walker—director of the Enteric Vaccine Initiative at PATH’s Vaccine Development Program—writes about how the double-mutant heat-labile toxin is a potential booster for much-needed new vaccines against diarrhea. The leading bacterial causes of diarrhea are enterotoxigenic Escherichia coli (ETEC) and Shigella, and vaccines against these pathogens could save the lives of up to a half-million children each year. PATH’s enteric vaccine project is working to accelerate the development of several promising vaccine candidates. We are also looking at innovative ways to make these vaccines as effective, practical, and affordable as possible so they can be easily implemented in the developing world. Adjuvants, ingredients that may enhance the effectiveness of some vaccines, are one important area of focus. PATH is currently involved in research on a highly promising new adjuvant, the double-mutant heat-labile toxin (dmLT), which could open more doors to achieving immunity in the intestine. The dmLT is actually an ETEC antigen (a substance that causes the immune system to produce antibodies against it), so it may offer protection against both diarrhea and intestinal infection when used in conjunction with vaccines that are targeted to mucosal surfaces like the intestine. We aren’t exactly sure why, but children in resource-poor countries often have a lower response rate to mucosal vaccines. A wide range of factors may contribute to this issue, such as the influence of breastfeeding and maternal antibodies, poor nutrition, or increased exposure to intestinal pathogens. An adjuvant like the dmLT may help to bridge this gap in effectiveness. Dick Walker with children in Cambodia. Promising vaccine technologies can help expand and improve the arsenal of tools to use in the fight against diarrhea among children. Right now, we’re working with the National Institutes of Health’s (NIH) Division of Microbiology and Infectious Diseases on a Phase 1 clinical trial using oral doses of dmLT (not in conjunction with a vaccine) in healthy adults. We will have complete results later this year, but the preliminary data are quite promising. Meanwhile, we are about to launch our first Phase 1 trial of the dmLT combined with one of our oral ETEC vaccine candidates. In addition, we plan to start another Phase 1 trial to test the dmLT intradermally (through the skin), and we would also like to study its use sublingually (under the tongue), to see if these alternative delivery routes can achieve an immune response in the intestine. If preclinical studies accurately predict what will be seen in humans, delivering dmLT in these ways could open up a whole range of possibilities for developing more effective and practical vaccines. This type of innovative research is critical to moving forward the field of vaccines to address diarrheal disease, and support from the NIH and other partners is critical to this effort. As the dmLT and other promising vaccine technologies progress in their development, we know we are getting ever closer to expanding and improving the arsenal of tools to use in the fight against this major killer of children.