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The answer is yes according to a group of 35 leading scientists who have come together to explore new strategies to accelerate vaccine development for deadly diseases such as malaria, HIV, tuberculosis (TB), and cancer. These scientists—who are part of planning a new initiative called the Human Vaccines Project (HVP)—hope that just as the Human Genome Project successfully mapped the building blocks of human life and led to numerous drug development and medical breakthroughs, a Human Vaccines Project could decipher the “human immunome”—providing a road map of the human immune system that would help scientists accelerate the development of vaccines for existing and emerging diseases. On Wednesday, Nature Immunology released a paper by researchers exploring the HVP that outlined the challenges to vaccine development, the opportunities presented by recent technological advances, and a broad vision for HVP’s future work. Could mapping the “human immunome” lead to the next generation of vaccines? Scientists hope yes. Photo: PATH/Aaron Joel Santos “A Human Vaccines Project focused on solving the major scientific problems impeding vaccine development could be transformative for efforts to help prevent these devastating infectious diseases as well as certain cancers,” said Wayne C. Koff, Chief Scientific Officer of the International AIDS Vaccine Initiative (IAVI) and lead author of the report. Vaccines are among the most effective interventions in the history of public health, having led to the eradication or near eradication of diseases like smallpox and polio and the collective prevention of 2-3 million deaths per year. However, scientists have not yet been able to develop broadly effective vaccines against a number of common and deadly diseases like malaria, AIDS, TB and cancer.   Why do vaccines for some diseases elude us? One of the reasons is because the viruses that cause these diseases are so complex and clever. Take for example variable viruses like influenza and HIV. These viruses behave sort of like characters from the Transformer movie. Like Optimus Prime, they constantly mutate, evolve, and change their form—making it difficult for scientists to develop a vaccine against them. Other viruses are just tough nuts for scientists to crack. For example, the respiratory syncytial virus (RSV)—which causes respiratory infection in infants—has mechanisms that not only block the immune system’s ability to signal to certain cells that it has been compromised, but also alters the immune system’s “memory” processes which typically allows it to react more quickly to subsequent exposure to the same pathogen. As a result, RSV re-infects people throughout their lives. Another challenge impeding vaccine development is the fact that different individuals’ immune systems respond differently to the same virus. In particular, the immune systems of infants and the elderly behave differently than those of adults, so a vaccine that works for adults may not work for either of these populations. In addition, our immune system can react haphazardly when it is assaulted from multiple fronts. For example, rotavirus vaccines are more effective in the developed world than in developing countries where people’s immune systems—as a result of poor sanitation, water and hygiene—are often already fighting off other infections. The opportunity and vision for a Human Vaccines Project Despite these challenges, the paper notes that scientific and technological breakthroughs over the last decade have introduced news tools and technologies that provide an opportunity to revolutionize vaccine development. An HVP would hope to exploit these technologies to change how vaccine development is undertaken. Drawing a parallel to the success of the Human Genome Project, HVP envisions a large-scale, highly collaborative effort—estimated at $1 billion over the next decade—that would bring together industry, government, academia, and nongovernmental organizations to work together to tackle the challenges outlined above. Part of the project’s approach will be a major effort to map the “human immunome.” What does it mean to map the “human immunome”? The human immune system is a series of cells with receptors that recognize and respond to the introduction of foreign substances into the body. It’s a complicated system with an enormous diversity of cells working together to weed out and attack viruses and infections. Traditionally vaccine research has focused more on results coming from experimentation for a specific disease, rather than on understanding the underlying principles of the immune system. Relatively little is known about the interaction of immune responses and cellular processes that provide immunity in response to a vaccination. In the past it would have been inconceivable to try to map the immune system because of the sheer number of genetically different cells involved, but due to improvements in genetic sequencing technologies and computer tools to manage and analyze large data sets, the paper’s authors now believe it could be possible to figure out the sequence of all those receptor cells in the human adaptive immune system. Like the Human Genome Project, such an initiative could take many years, but it would create an essential public tool with the potential to transform the science of vaccine development.

As the DC summer kicks into full swing, Congress has had a busy month moving forward fiscal year (FY) 2015 funding legislation for a variety of government programs including global health research and development (R&D). Global health R&D at USAID: Yesterday, both the House and Senate State and Foreign Operations (SFOPs) appropriations subcommittees held mark-ups of their draft bills. The House draft provides only topline spending numbers, with the addition of family planning/reproductive health, polio, the President’s Emergency Plan for AIDS Relief (PEPFAR), and the Global Fund funding levels. The House funded the overall account above the White House request, but below what was appropriated in FY 2014. Including the State Department and the US Agency for International Development (USAID) numbers, funding was $132 million below the numbers Congress appropriated in FY 2014, but a welcome $257 million more than what the White House had requested. For a quick comparison of numbers, check out the Kaiser Family Foundation’s SFOPs policy analysis. The other accounts called out in the House bill were $59 million for polio (the same as FY 2014, but 18 percent higher than the President’s request) and family planning at $461 million. Funding for family planning was a significant but not unexpected cut from both the FY 2014 number (24 percent cut) and the White House request (28 percent cut). As the full House appropriations committee has not yet marked up the bill (and it’s not clear that they will), details on the contents of the bill report’s priorities and other policy riders are not yet known. We do know the House bill reinstates the Mexico City Policy—which prevents nongovernmental organizations who receive federal dollars from promoting abortion services as part of family planning­—or prohibits any funding to the United Nations Population Fund (UNFPA). The full committee may take the bill up for consideration sometime next week. The Senate summary provides considerably more specific account figures for global health than the House bill. The Senate bill flat-funds the Global Fund and PEPFAR compared with FY 2014 and is even with the White House request—it’s interesting to note that for this overall account, the House bill appears to provide a higher funding level, even though we don’t yet know the exact funding distribution. Most other accounts were funded at levels either matching or slightly above FY 2014 funding. One exception is the tuberculosis (TB) account, which faces an $11 million cut from FY 2014 levels, although it is not as dire as the proposed White House funding level, which would have cut an additional $23 million. There is better news to be found for family planning and reproductive health, neglected tropical diseases, polio, and vaccine access. There’s no explicit word in either the House or Senate bills regarding the overall Maternal and Child Health account. NIH, CDC, and FDA Last week the Senate held its Labor, Health, and Human Services (LHHS) subcommittee mark-up and released a summary of their draft bill. A full Senate committee mark-up has yet to be scheduled, and the House has yet to move forward with its own draft bill. This account remains one of the most contentious, both because of ongoing efforts to alter the health care reform programs and because of a Senate plan to use the Overseas Contingency Operations account as a complicated and likely unsustainable mechanism to boost up funding for domestic priorities. The committee requested $30.459 billion for the National Institutes of Health (NIH), an increase to both the White House and FY 2014 levels by $324.0 million and $605.7 million, respectively, but still far less than the $32 billion needed. Global health programs within both NIH and the Centers for Disease Control and Prevention (CDC) also did quite well in the Senate bill—the CDC’s Centers for Global Health and Emerging Zoonotic and Infectious Diseases, the NIH’s National Institute of Allergies and Infectious Diseases (NIAID), and the Fogarty International Centers were nearly all funded at levels above both FY 2014 and the White House request. Both the House and Senate have also marked-up their legislation to fund the Food and Drug Administration (FDA). The House bill funds the FDA at $2.583 billion (this number represents budget authority and does not include user fees), which is a $23 million increase over FY 2014 and is about level with the White House request. The Senate bill funds the FDA at $2.588 billion, an increase of $36 million over FY 2014. The Senate is taking up this bill as part of a “minibus” along with the bills from the Commerce, Justice, and Science subcommittee, the Transportation subcommittee, and the Housing and Urban Development subcommittees. The Senate version of the bill also included some interesting report language around FDA’s international leadership to combat threats to global health and the global drug supply chain.  Defense The House Appropriations Committee approved their FY 2015 bill which essentially flat funds Department of Defense (DoD) R&D—which includes all research at DoD, not just neglected disease R&D—from FY 2014 levels. The American Association for the Advancement of Science provides a helpful summary of R&D funding within the draft bill which can be found here. The Senate Appropriations Committee has yet to mark-up a bill. In both the House and Senate, we see policymakers diverging from the priorities emphasized by the White House in its original budget request: there is little mention of any implementation of the infamous Opportunity, Growth, and Security account suggestions for global health or health research, although the Senate Appropriations Committee has developed its own plan for handling the declining budget caps while still supporting accounts they view as important to US health research programs. While the progress we’ve seen so far is commendable, Congress must speed its efforts to enact smart, evidence-based appropriations for global health R&D programs and their overarching accounts. As the end of the current fiscal year looms closer, policymakers must work together to avoid the stalemate that caused the government shutdown of the fall of 2013 and should support strong funding levels for global health R&D.

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Last week, the Center for Strategic and International Studies hosted a panel on the occasion of the release of its summary report, Strategic US Leadership—Essential to Address the Global Tuberculosis Pandemic, which examines US approaches to tackling tuberculosis (TB) both in the United States and abroad. The report concludes that the United States needs to better lead, coordinate, and prioritize its TB efforts, as well as create robust, long-term research partnerships with key institutions in select emerging economies to promote the discovery and development of new TB tools. GHTC member PATH has been awarded a three-year, US$15.6 million grant from the Bill & Melinda Gates Foundation to develop effective treatments for severe acute secretory diarrhea (ASD). The new grant will support a portfolio approach to drug development in an effort to maximize the chances of successful drug candidates to treat ASD, as well as support new engagement with the public and private sectors. Last week, the US House of Representatives introduced the End Neglected Tropical Diseases Act in an effort to turn the tide in the fight against neglected tropical diseases. The bill was introduced by Rep. Chris Smith (R-NJ) and already has bipartisan support from Reps. Matt Salmon (R-AZ), Hank Johnson (D-GA), and Greg Meeks (D-NY).   Osman Sankoh, executive director of INDEPTH, emphasized the important role of research and innovation for development in low- and middle-income countries (LMICs) in The Lancet Global Health Blog. Sankoh writes that “stronger international commitment to investing in research, development, and innovation in LMICs” is crucial in the post-2015 development agenda. He added that “research into health threats not only saves lives—it also helps governments and donors to save money.” Scientists at Imperial College London have created genetically-modified mosquitoes that produce 95 percent male offspring with the goal of helping control malaria. They believe introducing these mosquitoes into the normal mosquito population could lead to a shortage of females and a crash in overall population, thus reducing malaria incidences. GHTC member Aeras has released a new film exploring the TB crisis in the mines of South Africa. The film—called Undermined—looks at “the river of TB flowing out from the mines, and why a vaccine is critical to the global fight against this disease.”

  The development of new diagnostic, treatment, and prevention products is fundamental to accelerating the decline of the global tuberculosis (TB) burden, panelists from the World Health Organization (WHO), the National Institutes of Health (NIH), and the Bill & Melinda Gates Foundation agreed on during a panel discussion hosted by the Center for Strategic and International Studies (CSIS) on Monday. CSIS panelists say R&D is fundamental to meeting new global TB targets. Photo: PATH/Satvir Malhotra CSIS hosted the panel on the occasion of the release of its summary report Strategic US Leadership – Essential to Address the Global Tuberculosis Pandemic—which examines US approaches to tackling TB both in the United States and abroad. The report concludes that the United States needs to better lead, coordinate, and prioritize its TB efforts, as well as increase fiscal and other resources devoted to the issue. Among its recommendations, the report encourages the United States to create robust, long-term research partnerships with key institutions in select emerging economies to promote the discovery and development of new TB tools. During the panel discussion, Dr. Mario Raviglione—director of the global TB program at WHO—discussed the ambitious TB targets put forward in a World Health Assembly resolution including the goal of achieving 95 percent reduction in TB deaths by 2035. He noted that the model for achieving this target assumes the introduction of new TB diagnostics, medicines, or vaccines and said achieving this target will not be possible without investments in research and development (R&D) that result in the introduction of new interventions. The panelists agreed that while the United States will continue to drive efforts toward the development of new TB tools, middle-income countries and rising economies also have an important role to play as well. Dr. Peter Small—deputy director of the TB program at the Gates Foundation—noted that many of these emerging economies also have high TB disease burdens so they are uniquely positioned to contribute. Dr. Small said he believes that it is important for these nations to increase their R&D capacity and investments in science and that US leadership in fostering R&D capacity within these nations will prove key to the long-term development of more frugal and locally-viable TB products. Dr. Tony Fauci—director of the National Institute of Allergy and Infectious Diseases at NIH—agreed with Dr. Small’s statements regarding the need to forge TB partnerships and collaborations with our emerging economy partners. As an example of successful collaborations, he mentioned the increased use of co-principal investigator projects, where a researcher form the United States and a researcher from a different country collaborate on a research project with each of their home countries providing part of the funding. The panelists discussed not only the need for improved collaboration and coordination with other nations, but also the need for enhanced coordination within the United States. Dr. Fauci said while he believes there should be a concerted, coordinated R&D effort by the US government, it needs to be approached carefully. He said he believes fundamental research at the early stages needs to remain somewhat spontaneous, but that he sees a need for greater coordination downstream. A common theme throughout the discussion was the lack of adequate financial resources to meet the demands of a growing and complicated pandemic. Dr. Fauci mentioned the decreasing purchasing power NIH now as a result of stagnated federal funding over the last few years. He noted that as a result, NIH has less flexibility to jump on promising TB research. Dr. Fauci said he believes our country needs to reevaluate how we think about biomedical innovation and research funding—arguing that the US research budget should not be thought of as discretionary funding, but rather an item that needs to be automatically increased each year like cost of living increases. Panelists were also asked to consider the best arguments to convince US policymakers to increase investment in R&D for TB. Dr. Fauci said advocates should talk about how we live in a global community in which we can’t think of it as “our disease versus their disease”—that the United States has an economic and security interest in tackling TB. He also said the TB community should not see HIV as a source of competition for funding, but rather hold it up as an example of the impact that can be realized as a result of robust investments throughout the development process. Dr. Raviglione agreed, noting that within just a few years of the emergence of the AIDS epidemic, the world had already developed diagnostic tests and a few years later developed antiretroviral treatments. Dr. Raviglione said this is a very visible example of the results that can be achieved for a disease through strong investment in R&D.