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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.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. The White House Office of Science and Technology Policy and the Results for Development Institute have released new reports that examine incentives for global health research and development. Pharmaceutical company AstraZeneca and the Drugs for Neglected Diseases initiative have announced an agreement to collaborate on drug-compound screening for the neglected tropical diseases leishmaniasis, Chagas disease, and sleeping sickness. Todd Park, US chief technology officer, discusses innovation efforts undertaken by the US Government, including the Entrepreneurs in Residence Program at the US Food and Drug Administration. The Institute of Medicine has released a report on how to make clinical trials more efficient and effective.

Research!America, a GHTC member, recently hosted an event on global health research and development (R&D) in New York. In this guest post, Mandy Goldberg, MPH, shares highlights from the event. Research!America, in partnership with the AIDS Vaccine Advocacy Coalition (AVAC), Drugs for Neglected Diseases initiative North America (DNDi), Global Alliance for TB Drug Development (TB Alliance), International AIDS Vaccine Initiative (IAVI), SUNY Downstate Medical Center, and Treatment Action Group (TAG), hosted a forum, Global Health Research and Development in New York: Fueling Innovation and Saving Lives, on Monday, April 9, at the New York Academy of Sciences. Mary Woolley, president and CEO of Research!America, opened the forum by acknowledging the remarkable progress made in the growing field of global health research in New York in the past decade. She also released the results of a new state poll commissioned by Research!America that shows that 64 percent of New Yorkers are concerned about global health, and 63 percent believe that global health research is important to New York’s economy. Congresswoman Nita Lowey (D-NY-18) then took the stage and explained the significance of global health R&D as an economic driver that creates jobs for New Yorkers. She stated that “despite the critical importance and significant economic impact of these programs, funding for global health is threatened again this year” in regard to the proposed fiscal year (FY) 2013 budget, and pledged to continue fighting for “robust funding for all our global health programs, including critical research and development.” Renowned global health commentator Laurie Garrett, senior fellow for global health at the Council on Foreign Relations, moderated a discussion between panelists Rachel Cohen, regional executive director, DNDi North America; Jack DeHovitz, MD, MPH, distinguished service professor and director, SUNY Downstate AIDS International Training and Research Program; Margaret McGlynn, president and CEO, IAVI; Mel Spigelman, MD, president and CEO, TB Alliance; and Pol Vandenbroucke, MD, vice president of development, emerging markets, Pfizer. In her opening remarks, Garrett emphasized the importance of the US commitment to global health funding, especially after the 2008 financial crisis, when “the United States stepped up to the plate” after the community saw “a huge number of players disappear” from the field. She stated that “if we cannot protect the US commitment to global heath spending, every single program in global health is going to have to chop, chop, chop its budget.” Laurie Garrett moderated a panel including Mel Spigelman, Pol Vanderbroucke, Rachel Cohen, Margaret McGlynn, and Jack DeHovitz. Panelists then discussed how innovative partnerships among public, private, and academic sectors are transforming the way that research is conducted and yielding promising developments for the future of global health. Spigelman highlighted that the TB Alliance is “on the verge” of technological breakthroughs, which require an increased commitment to research due to the costly final stages of testing and clinical trials. Partnerships in global health R&D are cost-effective, he argued, citing the TB Alliance’s NC-002 clinical trial conducted in partnership with the US Agency for International Development, Bayer, and Novartis. This trial has the potential to produce a drug regimen that could reduce the TB treatment to 4 months, potentially saving as much as 90 percent of current costs. Vandenbroucke emphasized that the private sector has unique resources and capabilities to contribute to partnerships that are essential for the development of health technologies. He stated that cuts to the federal budget would affect the work of the pharmaceutical industry “in the long term, as less funds are available to do the basic groundwork to study diseases” that Pfizer then applies during its advanced drug development process. Cohen expressed concern over the fact that neglected tropical diseases (NTDs) received the single largest percentage funding cut of the global health programs in the President’s FY 2013 budget request and the impact this would have on DNDi’s work. She noted that there is currently no federal funding available for late-stage product development for NTDs, and the current FY 2013 budget request “totally eviscerates the possibility of future investments, at least for the coming 2 years,” if passed, which threatens the continued progress of DNDi’s efforts. McGlynn spoke about the evolution of IAVI from an advocacy organization to a product development partnership, with the support of Mayor Bloomberg and New York City. IAVI’s Vaccine Design and Development Laboratory, established in Brooklyn in 2006, plays a pivotal role in the Mayor’s New York City Bioscience Initiative and is a key component of IAVI’s global AIDS vaccine R&D network. McGlynn stressed that the scientific expertise of New York City’s “globally educated and raised” workforce has been essential to IAVI’s work, and to the growth of global health R&D in the area. DeHovitz reinforced that multisectoral collaborations have yielded major advancements in the field of HIV and AIDS. He cited the federal contribution to international HIV and AIDS through the work of the Fogarty International Center at the National Institutes of Health, which funds advanced research training in public health at five New York City universities. He also spoke of “the huge upsurge of interest among our health care students in global health,” stating that 45 percent of medical school entrants are interested in global health and 30 percent of medical school graduates have had a global health experience in school. “They’re committed, they’re interested and they want to help,” he said, noting the potential impact of this group to the future of global health. New York—home to seven of the top 50 US research universities, the largest bioscience workforce and second-largest life sciences workforce of any US city, and three global health product development partnerships (PDPs)—is clearly a world leader in global health R&D, and this growing industry is a promising economic engine for the state. There was a general consensus in the room that the community needs to work together to ensure that global health R&D remains a priority. Great progress has been made in the development of new technologies to fight TB, HIV and AIDS, and NTDs, and increased funding is needed to sustain this momentum and build upon previous successes. Spigelman noted that the current “slash and burn” Congress could have a devastating effect on global health efforts, and argued that the US will get “the most bang for that buck” by investing in global health technologies that will reduce the foreign aid budget in the long term. Woolley concluded the forum with a call to action, asking the global health community to share with others, including their members of Congress, the importance of the work that they do. A video of the event is available here. For more information on global health R&D in New York, check out the New York edition of Research!America’s economic impact state fact sheet and public opinion poll series.

Developing new medical products is a global enterprise, with research and development (R&D) activities spanning national borders and products being introduced in many countries at the same time. A critical part of this global R&D effort is the regulation of new health tools to help ensure that these products are safe and effective before they reach the populations who need them. In countries around the world, regulatory agencies play a critical role in this process, much like the US Food and Drug Administration (FDA) does for health products for American consumers. When creating new tools for diseases of the developing world, product developers sometimes face overlapping and conflicting regulatory processes that can dramatically slow the development and delivery of vital new products to help combat global health scourges like malaria, tuberculosis, and neglected tropical diseases. Delays in the approval of clinical trials can add years to the product development process and can significantly increase costs. Meanwhile, delays in the final approval of a product can lead to unnecessary suffering and death for patients who are unable to access the best possible tools for prevention, diagnosis, and treatment. There has been a lot of talk recently about ways to streamline and harmonize regulatory processes to reduce the time and cost of delivering new products. One such effort is the new East African Community’s (EAC) Medicines Regulatory Harmonization initiative, launched at the end of March in Arusha, Tanzania. Through this program, regulators from six agencies in five East African countries—Burundi, Kenya, Rwanda, Tanzania, and Uganda—as well as Zanzibar will work together to: Establish harmonized procedures for medicines registration. Build regional capacity in regulatory science. Increase access to lifesaving solutions for patients and communities. Representatives from disease-endemic countries, regulatory authorities including the FDA, product development groups, donors and technical partners, and other key stakeholders participated in the launch activities, showcasing the excitement over the steps underway in the region. Participants also highlighted what is at stake in the EAC’s efforts, which are seen as establishing a path forward for other harmonization efforts in regions across Africa and around the world. Over the next several years, support for these efforts—in the form of technical assistance, training opportunities, and political backing—from the FDA and other experienced regulatory authorities will be crucial. The FDA has a vast amount of expertise that can be leveraged to benefit this new initiative, and supporting the EAC would add to recent efforts at the FDA to become increasingly involved in global health issues. By supporting the new EAC regulatory initiative, the FDA can help to make a real impact on the health of patients in East Africa through the delivery of better and safer medicines in the region.