Breakthroughs Blog: NIH

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.

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.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. The Consultative Expert Working Group on Research and Development: Financing and Coordination (CEWG) has released its final report. The report offers recommendations to close the funding gap in global health research and development. The Fogarty International Center and other programs at the National Institutes of Health are awarding about $20.3 million over the next five years to train the next generation of global health researchers and scientists. The US Agency for International Development (USAID) has released a new policy that aims to ensure the quality and integrity of the agency's scientific activities. The report recognizes that USAID is the US Government’s “lead international development agency, for which science and technology are critical means for improving the quality of peoples’ lives around the world.” A new study offers insight into promising new targets for future HIV vaccine efforts.

In this feature on Breakthroughs, we provide an update on what’s currently happening with global health in Congress and an outlook for future legislative activity. Foremost on Congress’ plate this week was, of course, the appropriations process. Last week, House Budget Committee Chair Paul Ryan (R-Wisconsin) released his fiscal year (FY) 2013 budget resolution, which the House Budget Committee has now approved by a 19-18 vote. The full House passed the resolution yesterday 228-191, making the appropriations process even more complicated, as the legislation conflicts with much of the Budget Control Act (BCA) signed into law last year. In the resolution, international affairs funding in the approved resolution totals $49.1 billion. This is a reduction of $7.1 billion, or 12.6 percent, compared with President Obama’s FY 2013 requested funding levels. A report accompanying the resolution outlines some potential cuts that could help achieve this $7.1 billion cut. The section that covers the State and Foreign Operations account does not mention any global health-specific policy changes, so it is unclear at this stage how global health, as well as research and development for new health tools, would fare under Ryan’s resolution. Regardless of the House’s approval, the resolution will be dead on arrival in the Senate. House Democrats introduced their own budget alternative, authored by Maryland Democrat Chris Van Hollen. Their approach follows what President Obama requested fairly closely, but both this alternative as well as a more conservative resolution—supported by the Republican Study Committee—did not garner the votes needed to pass. Also this week, the National Institutes of Health (NIH) Director Francis Collins testified before the Senate Appropriations Committee. When he spoke at a similar House hearing recently, the new National Center for Advancing Translational Sciences (NCATS)—which Collins stated has the potential to support the development of new tools for rare and neglected diseases—was a hot topic, and the same was true with the Senate. Collins was questioned on plans for future projects at NCATS, and whether they would affect the NIH basic research budget. The effect of across-the-board federal budget cuts on the NIH was discussed during the Senate hearing, with Collins stating that there would be hundreds of great research projects that would not be funded if these widespread cuts take place. You can read testimony from Collins—as well as National Institute of Allergy and Infectious Diseases Director Anthony Fauci and other NIH leaders—here. Now that most of the hearings have been completed on the President’s budget request, appropriations committees in both the House and Senate will soon move to approve legislation for all accounts in the federal budget. It’s likely that the House subcommittee will start to approve funding legislation in May, with the Senate following suit shortly after. The process is moving along normally—for now. With growing anxiety about whether Congress will alter the required across-the-board budget cuts, and the Presidential election drawing closer, we may still see a replay of previous years’ deadlock.