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Mark Alderson, PhD, is the director of the pneumococcal vaccine project at PATH , a nonprofit international organization based in Seattle, Washington, specializing in global health. In this guest post, he writes about PATH’s efforts to develop new vaccines to fight pneumonia among children. In honor of World Immunization Week, the global health community is coming together to engage in immunization campaigns, advocacy, and awareness activities to bring the power of vaccines into the spotlight. Vaccines are one of the most successful and cost-effective technologies that prevent childhood mortality. According to the World Health Organization, immunization prevents between two and three million deaths per year. Regardless, many vaccine-preventable diseases continue to take lives unnecessarily because of gaps in vaccine research and development (R&D) that neglect developing-world needs. Barriers to vaccine access also prevent low- and middle-income populations from receiving the protection they need. Pneumonia—the number one killer of children under five years of age worldwide—is one such disease for which vaccines and treatments could save millions of lives. However, achieving sustainable global health impact over the long-term requires further investment in new vaccines that cater specifically to the developing world, where pneumonia hits hardest. To this end, public-private sector partnerships are essential to maximizing resources and speeding development. In the fight against pneumonia, we have reason to celebrate. Overall, investments in combating pneumonia have helped contribute to a 35 percent reduction in child mortality since 1990—no small feat. We have vaccines for several top causes of the disease, including the pneumococcus bacterium, which is the most common cause of severe childhood pneumonia and takes the lives of an estimated 800,000 children annually. Pneumococcal vaccines, having been accessible in the industrialized world for over a decade, are now rolling out in low-resource countries with the help of the GAVI Alliance and other groups. This month, Ghana is making history by becoming the first GAVI-eligible country to introduce two vaccines simultaneously—pneumococcal and rotavirus vaccines. The power of vaccines is evident, but unless we continue to invest in new vaccine tools that can provide better, more affordable protection, our ability to protect our children will be incomplete. Photo credit: PATH Despite these great strides, we must not forget that there is still a long way to go. The pneumococcal vaccines in use today are effective against certain varieties of the bacterium, but no vaccine yet exists that can protect against all of the more than 90 pneumococcal strains, leaving children susceptible to strains not covered by these vaccines. Also, current pneumococcal vaccines are relatively expensive, making them difficult for low- and middle-income countries to afford without substantial assistance from international donors. To fight pneumonia, which takes the life of one child every 20 seconds, we must waste no time in striving for broadly effective and affordable vaccines that can be sustainably accessible in even the most impoverished regions of the world. Because market forces alone are not always strong enough to drive the development of vaccines most urgently needed in lower-income countries, PATH is stepping in to help fill the gap. Our pneumococcal vaccine project is advancing R&D for new, low-cost pneumococcal vaccines that are tailored to meet the needs of children in the developing world. We collaborate with an array of public- and private-sector partners on vaccine R&D projects, including universities, research institutions, vaccine manufacturers, and biotechnology companies. We also work with US and foreign government agencies on epidemiology, vaccine research, and regulatory issues. Several of the vaccine candidates we support could provide broad protection against pneumococcus by using proteins that could help the body’s immune system recognize and defend against virtually all pneumococcal varieties. If successful, these vaccines could change the face of pneumococcal disease by providing universal protection at low cost. For candidates ready to enter clinical trials, we coordinate closely with the US Food and Drug Administration (FDA) to ensure compliance with regulatory requirements. We are also partnering in India to develop a vaccine candidate using technologies similar to current pneumococcal vaccines, but at significantly lower inherent cost. This vaccine candidate targets only pneumococcal varieties common in the developing world. If successful, India could become a global manufacturer of pneumococcal vaccines, blazing the trail for endemic country vaccine producers in a market previously occupied solely by European and US manufacturers. Recognizing that successful vaccine development requires access to a full spectrum of scientific resources, we also support research that advances the vaccine field at large. Among our various research partnerships are several with the US Government, including FDA and the US Centers for Disease Control and Prevention. Collaborations of this nature are essential to helping lay the scientific groundwork for new pneumococcal vaccines to come to fruition. The power of vaccines is evident, but unless we continue to invest in new vaccine tools that can provide better, more affordable protection, our ability to protect our children will be incomplete. Tackling prolific killers like pneumonia in the developing world is a critical step toward truly making an impact on the global burden of disease. Working in partnership here in the United States and abroad can help get us there sooner rather than later.

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.