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For the second time, the World Health Assembly took place in the midst of an ongoing pandemic that is widening health inequities across and within regions. More than a year after the first wave of the pandemic, health systems in many parts of the world continue to battle waves of infection amid shortages of oxygen, vaccines, and health care workers. Yet among the numerous challenges posed by the pandemic, there were positive signals that with coordinated and focused action, health innovation in record pace is possible, particularly if that action can be built on a firm foundation of existing research and development (R&D). Our next challenge—as we continue the battle against COVID-19 and other health threats—is to channel similar coordinated, focused action to ensure the benefits of innovation are distributed equally across both geography and gender. What happens when years of existing research systematically exclude certain populations, denying them or delaying access to the benefits of health innovation? How can we address the underlying causes and accelerate shifts to make clinical research more inclusive? A recent side event at the 74th World Health Assembly, co-organized by Deutsche Stiftung Weltbevölkerung, Global Health Technologies Coalition, and Medicines for Malaria Venture (MMV), explored the above questions by highlighting the specific issue of gender inequity in health innovation. The panelists at the event discussed how gender biases have resulted in women’s underrepresentation in preclinical and clinical research, leading to downstream gaps in therapeutic options for them. Though gender inequity in health innovation is not limited to malaria, this article builds upon MMV’s presentation at the event, focusing on gender equity in malaria R&D to meet unmet needs. Unlike COVID-19, malaria is a disease that we have known for centuries. Despite the vast amount of scientific and epidemiological knowledge on malaria, a quick glance at the historical trajectory of malaria research reveals that it has been embedded in a larger context of gender bias in medical research. During the clinical development of most new medicines, including antimalarial drugs, pregnant people are actively excluded from trials and, if pregnancy occurs during the trial, treatment is discontinued and follow-up on the pregnancy outcomes is ensured. While this practice aims to protect the pregnant person and the fetus, it also prevents the generation of data and in doing so it has created knowledge gaps in the treatment of malaria in pregnant people. In addition to delaying the benefits of new treatments to these populations, the knowledge gaps also hinder the creation and implementation of gender-sensitive policies to fight the disease.Malaria in pregnancy, and more broadly in people of reproductive potential, remains a major public health challenge today. The World Health Organization estimates that 12 million pregnancies are at risk annually, resulting in nearly 822,000 children being born with low birth weight. Though preventive tools like vector control (for example insecticide-treated bednets and indoor residual spraying) and intermittent preventive treatment in pregnancy exist, there are very few treatment options for pregnant and lactating people in their first trimester. The longer we wait to change our course, not only do we risk losing thousands of pregnant people and babies to a treatable disease, but we also widen the existing knowledge gaps that urgently need to be bridged. In other words, if we delay the process of integrating a gender lens as an essential element of the drug development process, the journey to catch up will be steep and could jeopardize efforts to eliminate and eradicate malaria. Fortunately, there is a growing determination within the malaria community to rectify gender-related data gaps. At MMV, we are doing so through our Malaria in Mothers and Babies (MiMBa) strategy, which aims to systematically prioritize and address the needs of pregnant people and newborns, right from target product profiling at the outset of drug development through to ensuring a stable supply of recommended medicines to treat and protect these populations from malaria. In one example, recognizing the lack of safety and tolerability data for antimalarials used during pregnancy, we have teamed up with the Liverpool School of Tropical Medicine to develop a pregnancy registry to help fill the data gaps with the objective of eventually establishing standard protocols in the treatment of malaria during pregnancy in all endemic regions.Other organizations, like the WorldWide Antimalarial Resistance Network, are building online repositories of published and unpublished literature on malaria in pregnancy, contributing to the methodical archiving of data on this topic. Furthermore, awareness campaigns like “Zero malaria starts with me” are also placing a strong focus on the need for inclusive innovation to treat malaria in pregnancy.In an important step forward, high-level decision-making bodies like the G7 are also taking note of this issue. We welcome the G7 health ministers’ Therapeutics and Vaccines Clinical Trials Charter to pave the way for “stronger collaboration in large-scale international trials to enable greater diversity of participants, including pregnant people and children.” This is an important step forward toward more equitable clinical research.While great strides are being made in advancing health innovation to better represent and account for the needs of all genders in health care, much critical work remains to be done. Decades of exclusion from clinical research will not disappear overnight. The need of the hour is gender mainstreaming supported by significant investments into R&D, as well as moving policymaking forward, to ensure a fairer and more inclusive health care system for all. Most importantly, while organizations like MMV commit to extend the benefits of our innovation equitably to all populations affected by malaria, we firmly believe that the road to achieving gender equity in clinical research will be paved by the inclusion and support of patients, health workers, researchers, policymakers, as well as the champions and advocates for health equity in the global health system. Much like for the COVID-19 pandemic, catalyzing this transition to a gender-sensitive malaria eradication strategy will require focused and coordinated action and all voices have a part to play.

In late May, the Biden-Harris administration released its detailed fiscal year 2022 (FY22) budget request. While the budget proposes significant, and welcome, boosts in funding to US health and research agencies—including the National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), and the Biomedical Advanced Research and Development Authority (BARDA)—and global health security programming at the State Department and US Agency for International Development (USAID), it falls short in its proposals to address long-standing global health challenges, where it largely proposes flat funding across key global health funding lines. Below we break down the details of the proposal and initial takeaways of how, if enacted, it could impact global health research and development (R&D) programming. State & USAID Global Health Programs In its budget narrative, the Biden-Harris administration touts plans to build on the global health sector’s “demonstrated success” and ensure we are “better prepared to prevent, detect, and respond to future biological threats and pandemics.” It recommends $10 billion in funding for USAID and State Department Global Health Programs—an $855 million, or 9.3 percent, increase over FY21 enacted spending—which is welcome news. Yet as you dive deeper into the proposal, it is clear one issue has risen to the top of the administration’s priority list: global health security. Of the $855 million overall proposed increase, $805 of it, or roughly 97 percent, is directed to health security–related funding lines. This includes $250 million for a new Global Health Security line under the State Department’s Global Health Programs to support a “new health security financing mechanism, which would be developed alongside U.S. partners and allies” and $555 million for USAID’s Global Health Security line. These investments could be transformative and are vitally needed as partner nations work to shore up their health systems to respond to COVID-19 and prepare for future health threats, and the new financing mechanism could support countries in strengthening their R&D capacity. Yet, it is discouraging to see the proposal largely overlook other pressing global health needs. Outside global health security, only two other Global Health Programs funding lines—USAID Maternal and Child Health and USAID Family Planning—receive any proposed increases, and they are modest at $24 million and $26 million, respectively. All other programs and lines are level funded compared to FY21 enacted funding. This was disappointing given most funding for global health R&D at USAID is from these disease/health-area lines, and implementers need additional resources as they face the compounding costs and challenges of maintaining existing research and service delivery programs, while simultaneously battling COVID-19. For more USAID and State budget details, view the chart below. FY21 Enacted 2022 WH Request 2022 WH Request v. 2021 Enacted (%) 2022 WH Request v. 2021 Enacted ($) USAID Global Health Programs $3265.95 $3870.95 +$18.52% +$605 Tuberculosis $319 $319 0% $0 Malaria $770 $770 0% $0 HIV/AIDS $330 $330 0% $0 Maternal & Child Health $855 $879 +2.81% +$24 Nutrition $150 $150 0% $0 Neglected Tropical Diseases $102.5 $102.5 0% $0 Vulnerable Children $25 $25 0% $0 Global Health Security $190 $745 292.11% $555 Emergency Reserve Fund - $90 - $90 Family Planning – all $575 ($233.95 for USAID FP) $483.7 ($550 for USAID FP) 1.1% (4.97% for USAID FP) $8.7 overall ($26.05 for USAID FP) State Global Health Programs $5,930 $6180 4.22% $250 PEPFAR $4,370 $4,370 0% $0 Global Health Security - $250 - $250 Global Fund $1,560 $1,60 0% $0 Global health R&D at NIH, CDC, and BARDA In response to the COVID-19 pandemic and both the scientific promise and public health perils it has exposed, the administration put forward a budget proposal for Department of Health and Human Services subagencies aimed at delivering “a new generation of medical breakthroughs” and “improving America’s public health infrastructure.” Most notable in terms of sheer funding, the budget proposes a $9 billion increase to the NIH budget, of which $6.5 billion, or nearly two-thirds, would go to support the launch of a new Advanced Research Projects Agency for Health (ARPA-H) within NIH. Likely to follow a similar model as the Defense Advanced Research Projects Agency, or DARPA, this proposed program would focus on advancing riskier, transformative breakthrough health innovations that would be unlikely to advance through the private sector alone. While ARPA-H was initially proposed by advocates as a potential mechanism to address market failures in R&D, implying it could touch on neglected global health areas, the president’s budget proposal specifically mentions a focus on cancer, diabetes, and Alzheimer’s, suggesting a narrower initial scope that would likely not encompass poverty-related and neglected diseases. Outside ARPA-H, the budget proposes more modest increases to NIH institutes and programs key to global health R&D, including a proposed 2.9 percent increase to the National Institute of Allergy and Infectious Diseases, where most emerging and neglected disease research takes place within NIH, and a .32 percent increase to the Office of HIV/AIDS. In very welcome news, the budget proposes a 14.6 percent increase to the Fogarty International Center, a center devoted to strengthening international research capacity, reflecting calls by GHTC and other advocates. Beyond NIH, the administration proposes a 10.5 percent, or $825 million, increase to the CDC budget, seeking to reverse a decade-long stagnant budget for the agency. Within that, there is a proposed 17.7 percent, or $105 million, increase to the Center for Global Health (CGH). However, mirroring similar trends seen in USAID and State funding, $100 of that $105 million increase is for global health security–related programming via the Global Public Health Protection line. The remaining $5 is for the CGH Division of Parasitic Diseases and Malaria, which is a welcome addition given this division has been flat funded for years. All other CGH funding lines remain flat funded. The National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), which has supported development of diagnostics and vaccines for infectious disease threats, also receives a proposed $30 million or 4.6 percent increase. Finally, the budget proposes a $226 million, or 37 percent increase, for BARDA to support the development of drugs, vaccines, and other medical countermeasures against public health threats. BARDA, which has been at the center of the US government’s COVID-19 R&D response, faces a dual mandate covering both man-made and naturally occurring health threats, but the latter part of its portfolio has been historically underfunded and over reliant on emergency funding. While GHTC has advocated for a new funding line at BARDA specifically for emerging infectious diseases and other naturally occurring threats, we welcome this overall funding boost, which will allow the agency to pursue a more forward-looking, robust portfolio in this space. For more NIH, CDC, and BARDA budget details, view the chart below. FY21 Enacted 2022 WH Request 2022 WH Request v. 2021 Enacted (%) 2022 WH Request v. 2021 Enacted ($) NIH $42,934 $51,953 21.01% $9,019 NIAD $6,069.619 $6,245.926 2.9% $176.31 Office of AIDS Research $3,090 $3,100 .32% $10 National Center for Advancing Translational Sciences $855.421 $878.957 $2.75% $23.54 National Institute of Child Health and Human Development $1,590.337 $1942.117 22.12% $351.78 ARPA-H - $6,500 - $6,500 Fogarty International Center $84.044 $96.322 14.61% $12.28 CDC $7,874.804 $8,700.00 10.48% $825.20 CGH $592.843 $697.843 17.71% $105 Global Immunization Program $226 $226 0% $0 Global AIDS Program $128.421 $128.421 0% $0 Global Tuberculosis Program $9.222 $9.22 0% $0 Parasitic Diseases and Malaria $26 $31 19.23% $5 Global Public Health Protection $203.2 $303.2 $49.21% $100 CDC-wide Infectious Disease Rapid Response Reserve Fund $10 $35 250% $25 NCEZID $648.272 $678.272 $4.63% $30 BARDA $596.7 $823 37.93% $226.30 While the president’s budget request provides a mixed picture for global health research advocates, with bold transformative investments for global health security paired with primarily flat funding for other critical health areas, it is ultimately up to Congress to decide our nation’s spending. GHTC will continue to track the appropriations process and engage with Congress to push for funding bills that meet the full spectrum of global health research needs.

Awaiting a chance to prove themselves, key technological advances that enabled swift development of vaccines against SARS-CoV-2 stood by for years before the pandemic struck. Chief among these were mRNA-based vaccines, which stalled in early-stage development. Research funders questioned the scientific merit of novel immunological approaches; major vaccine producers doubted their profit potential. Nevertheless, a handful of innovation-seeking public-private development partnerships, fueled by hard-won support, drove novel vaccine platforms forward just as SARS-CoV-2 gripped the world.As with much else, the COVID-19 pandemic upended vaccine research and development (R&D), leaving the world’s largest vaccine makers to play catch-up with smaller companies focused on vaccine innovation. Biotech start-ups capitalizing on cutting-edge technologies increasingly are driving vaccine development, which in turn is shedding its image as an investment backwater. Maintaining this momentum through ongoing investment in technological innovation can drive breakthroughs to thwart future pandemic threats, as well as endemic diseases that kill millions each year.During the early months of the historic rollout of vaccines to fight COVID-19, the Sabin Vaccine Institute’s Influenzer Initiative asked experts and innovators specifically to reflect on the past, present, and game-changing future of mRNA vaccine protection against a range of viral threats, including influenza. Exciting insights from these conversations are featured in the initiative’s latest video episode. As several of those interviewed attest, mRNA vaccines exemplify how basic discovery research coupled with targeted translational investments remain the engine of transformative innovations that save uncountable lives and immeasurably improve their quality. Eric Topol, founder of Scripps Research Translational Institute, observes that investments in immunology, virology, and molecular and structural biology provided the foundation for the rapid development of successful vaccines against SARS-CoV-2. David Topham, the founding director of the Translational Immunology and Infectious Diseases Institute at the University of Rochester, notes that vaccine platforms that have delivered us out of the current pandemic were enabled by targeted investments in nanoparticle technology.  Innovations like the COVID-19 vaccines provide benefits that extend far beyond their initial targets, such that every dollar spent on R&D yields five in return, notes economist Benjamin Jones of Northwestern University. In the case of mRNA vaccines, that beneficial ripple effect may include disarming the next pandemic threat. “Today we need methodologies that we can rapidly adapt so that when a new pathogen arises, we can make a vaccine against it,” says Teresa Lambe of Oxford University. That’s a key advantage of the mRNA platform, according to Topol. “mRNA does appear to have the ultimate flexibility,” he observes. “You go from sequence to template in a matter of hours.” SARS-CoV-2 demonstrates the value of this nimble technology, as the triumphant achievement of astonishingly effective vaccines remains threatened by the rise of potentially evasive variants—a long-standing challenge in building defenses against the next influenza pandemic.The challenges and consequences of inequitable access to vaccines has never been more sharply evidenced than by the current pandemic. The relative simplicity of mRNA vaccine manufacturing, as compared with that of traditional vaccine approaches, offers the potential to make vaccines when and where viral threats emerge and more readily available to the people who most need them. Vaccine manufacturing processes should be designed to be globally adaptable, Lambe argues. “All low- to middle-income countries, in fact all countries, should have the ability to make vaccines for themselves and to supply worldwide,” she says. Rajeev Venkayya, of Takeda Pharmaceutical Company, adds that decentralized vaccine production offers benefits beyond those provided by vaccines themselves. He describes how countries new to vaccine manufacturing could “leapfrog” into cutting-edge technology via mRNA vaccine production and build a new ecosystem for vaccine research, development, and distribution. The full potential of mRNA vaccines thus extends far beyond quashing pandemics. Developed and produced according to national or regional needs, mRNA vaccines can create innovative opportunity and healthier futures for people everywhere.Decades will be spent taking the measure of the COVID-19 pandemic: calculating its toll in multiple metrics, defining its vast and diverse lessons, and recognizing the changes it catalyzed. During that time, viruses with potential to cause even greater destruction will emerge. As the recent declaration of G7 leaders emphasizes, we must act now to develop transformative, adaptable, and affordable technologies to meet these threats—a declaration that George Gao, director of the Chinese Center for Disease Control and Prevention, insists must produce action. Among the pursuits he advocates is the exploitation of recently proven vaccine technologies to prevent another pandemic. “mRNA plus nanoparticle vaccines are two important routes for the development of novel influenza vaccines,” he says. Novel vaccines that enable robust, globally accessible disease prevention are within reach, according to Amesh Adalja of Johns Hopkins University. “I don’t think we’re going to be left in such a position with future emerging infectious disease emergencies,” he concludes. We take courage from these words, and those of Venkayya, who expressed his hope “that people will seize this moment to recognize that we could potentially avert the next pandemic.” 

Interested in more global health innovation news? Every week GHTC scours media reports worldwide to deliver essential global health R&D news and content to your inbox. Sign up now to receive our weekly R&D News Roundup email. Leaders of G7 countries committed this weekend to sharing at least 870 million COVID-19 vaccine doses with countries around the world. More than half of the doses will come from the United States, which the Biden administration announced earlier in the week would buy 500 million Pfizer doses, 200 million of which will be distributed by the end of this year followed by 300 million by next June, all through the COVAX vaccine-sharing facility. The United Kingdom pledged to donate 100 million doses, the first 5 million of which will be shared in the coming weeks. France and Germany will each share at least 30 million doses. The announcement comes as inequities in vaccine supply around the world have become more pronounced, and G7 leaders have faced increased pressure to outline global vaccine-sharing plans.The COVID-19 vaccine developed by Johnson & Johnson appears to be effective against leading virus variants, according to a new study published in Nature last week that looked at immune responses in the blood of vaccinated individuals. While data did show a reduction in neutralizing antibodies to the Beta and Gamma variants, researchers also noted that there are several other types of immune responses, including binding antibodies, FC functional antibodies, and T-cell responses. T-cell responses, which are critical in keeping an infection from spreading, were not reduced to the Beta, Alpha, or Gamma variants, according to the research. Studies have shown similar results with the Pfizer/BioNTech and Moderna COVID-19 vaccines. Researchers are continuing to evaluate vaccine-induced immune responses against variants, including how long the T-cell response lasts.The use of Wolbachia-infected mosquitos reduced cases of dengue fever by 77 percent in a clinical trial conducted in Yogyakarta, Indonesia, new data shows. The findings also showed an 86 percent reduction in hospitalizations due to dengue fever. The trial, conducted by the World Mosquito Program, used mosquitoes infected with Wolbachia bacteria, which reduces virus replication inside mosquitoes, limiting their likelihood of passing on dengue infection. Wolbachia can also alter the fertility of their hosts to ensure they are passed on to the next generation of mosquitoes, providing continued protection against dengue infection. The trial will be expanded across the whole city and surrounding areas, with the aim of eradicating dengue in the region.