Picking up the pieces

Glenda Gray was distraught in early March.

“We’re all gutted: there’s desperation, you know,” she says. “There’s disbelief. There’s huge sadness.”

As head scientist at the South African Medical Research Council, Gray is program director of the BRILLIANT Consortium, which was poised to launch a Phase I trial for an HIV vaccine candidate in early 2025. In mid-January, BRILLIANT was a broad and collaborative partnership of African researchers working to develop an HIV vaccine with support from the U.S. Agency for International Development (USAID). Just weeks later she had received notice that the U.S.$45 million in grant funding from the now-dismantled USAID was gone: first frozen, then gone for good.

Gray’s group was in the midst of several HIV vaccine research projects. They were negotiating deals with Indian manufacturers to evaluate novel vaccine formulations and immunogen designs and were working with self-amplifying mRNA. They had several ongoing collaborations with U.S. institutions, including Duke University and Harvard. USAID also funded work Gray and her colleagues were involved in on microbicides and long-acting antiretrovirals, and another clinical trial and research partnership called ADVANCE (Accelerate the Development of Vaccines and New Technologies to Combat the AIDS Epidemic, administered by IAVI), which was also terminated after funding administered through USAID ended abruptly.

“It’s all a huge blow to us because this work allows us as African scientists to set the agenda and direct clinical development programs. If we lose that, we lose our ability to influence the field and make a difference. And it’s devastating from a vaccine development point of view and in capacity development, especially for technology transfer and laboratory infrastructure. It’s horrible for us,” she says.

New administrations often change how much federal funding flows into biomedical research or which research initiatives are prioritized. But the funding, policy, and staffing changes to foreign aid and domestic biomedical research programs within the U.S. in the past 100 days may be among the most rapid and dramatic ever seen.

“Both the pace and the magnitude of the transformations and disruptions in every aspect of the federal government’s efforts around biomedical research, disease prevention, and biomedical regulation really are unprecedented,” says Jason Schwartz, Associate Professor of Health Policy at the Yale School of Public Health. “The changes we’ve seen in the last few months in terms of personnel, approaches, priorities, and signals are dramatic.”

These changes are sending shockwaves through government, academic, and non-profit organizations engaged in many disciplines of scientific research, everything from environmental science to public health research. “There is a climate of uncertainty regarding the future of the federal government’s interest in, commitment to, and investment in biomedical research, and vaccines, in particular,” Schwartz says.

His research focuses on vaccination policy. He also serves in the history of medicine department at Yale Medical School and so is well-versed on the U.S. government’s historical role in supporting the development and deployment of vaccines to promote public health, as well as the reticence among some sectors of the public to accept them. Vaccine skepticism isn’t new — Schwartz says people have questioned both the safety and efficacy of vaccines for more than 200 years. Opposition to government-mandated vaccination programs isn’t new either. What is new is the shifting attitude toward vaccines from within the federal government. And this, Schwartz thinks, may be one of the biggest threats to human health.

“There have always been concerns around vaccines, but they came from across the ideological or political spectrum. Now, the challenges to what we know and understand about the value of vaccines are coming, in large part, from the leaders of our core public health agencies, including the Secretary of Health and Human Services, who, throughout his career, has been one of the most prominent skeptics and critics of our current understanding of the value and benefits of vaccines,” he says.

“The distrust in public health, distrust in public health expertise, and sadly, the skepticism toward the value of vaccines has become an increasingly mainstream position of right-leaning voters and politicians, even though the importance of vaccines remains every bit as strong. That creates a real grave threat to the bedrock support for vaccination programs. It’s hard to sugarcoat it.”

This threat to vaccination programs comes as the U.S. is battling a measles outbreak. Only four months into the year, the total number of measles cases is already more than triple last year’s total caseload. Rates of pertussis are also soaring as vaccination rates decline.

Internationally, vaccination programs also face major challenges. The dismantling of USAID will not only impact global vaccine research efforts, including Gray’s work in South Africa and the research agendas of many other groups, it will also certainly disrupt vaccine delivery programs. The aid agency was a major funder of Gavi, the Vaccine Alliance, an organization that funds the purchase and distribution of lifesaving childhood vaccines in less wealthy countries. Gavi rescheduled its previously scheduled replenishment — a five-year ask for $9 billion — to June.

The World Health Organization (WHO), the leading global multilateral health institution, is also facing major cutbacks that will likely affect its efforts to support pandemic preparedness and infectious disease epidemiology and surveillance. In January, the White House announced it intends to withdraw U.S. support from the WHO. The organization is set for perhaps a 40 percent staff reduction in its Geneva headquarters and is projecting a $1.9 billion budget gap for 2026-2027.

Across public-health, academic, and government institutions, researchers are grappling with drastic changes in funding. Funding gaps will likely mean a re-prioritization within many fields: particularly within HIV research. The extent of these changes isn’t fully apparent yet. For now, many researchers are focusing on finding new, sustainable sources of funding to support their work, which they maintain is as important as ever.

Gray’s team is already moving to plan B, which is continuing the work but modifying their plans and calling on African governments and the private sector to step up their support of these projects. The vaccines for the Phase I HIV vaccine trial under the BRILLIANT consortium are in cold storage. “We could get co-funding for an abbreviated trial, so we are working on that. In terms of the larger program, we are going to have to put it together piecemeal because we are not going to get one big funder that will pick it all up. We are going to have to be a lot less ambitious.”

But Gray is not planning to reorient her approach to HIV vaccine research, nor does she think anyone else should.

“The scientific goals and questions should not change. I think we need to find other ways to support this, non-traditional funders, other philanthropists, European agencies or those in Japan or South Korea. Are there other people that are interested in finding an HIV vaccine? How do we galvanize those groups?”

So, she presses ahead.

In Cape Town, Petro Terblanche, chief executive at Afrigen Biologics — also part of the BRILLIANT consortium and the base for the WHO’s drive to bring mRNA-based vaccine development to sub-Saharan Africa — is also doing her best to manage the current uncertainty. “My organization and many affected by these kinds of decisions invest years and years of knowledge and the facilities to create a product or solution. It’s not a switch you can just flip on and off,” she says. “I hope the current very dynamic change will settle as soon as possible and provide some clarity. What will be funded? What will be prioritized?”

The harshest and most immediate impact is on frontline services, she says. Longer-term projects, such as HIV vaccine development and mRNA manufacturing platforms, will require prioritization. “We at least have the opportunity to take a step back and do some re-planning.” But this doesn’t mean these areas won’t be hit hard. “The impact on Afrigen is huge. We have to decide on whether to continue with further development in HIV or to find other funding sources,” she adds.

It may also mean redirecting resources. “We’re not a dedicated HIV product development entity. We are a platform. But this platform, which is critical for pandemic preparedness and pandemic response, needs to be sustained by multiple products.”

In European vaccine research laboratories, the mood is less gloomy, but researchers remain cautious. Tomáš Hanke, a vaccine immunologist at the Jenner Institute in Oxford, says his HIV vaccine programs are, so far, proceeding without delay.

He and his colleagues are either preparing for or are already involved in several small-scale early-phase clinical trials in sites in the U.S., Europe, South America, and Asia. There are 10 all told, all using a similar experimental formulation called HIVconsvX. It is a chimpanzee adenovirus-and-poxvirus MVA-vectored four-component conserved mosaic HIV T-cell vaccine candidate that is being tested in combination with some HIV cure strategies involving both antibody infusions and immunomodulators.

The virologist Rogier Sanders at the University of Amsterdam’s Academic Medical Center, alongside colleagues in New York and San Diego — among others — is continuing to pursue a complex path to inducing broadly neutralizing antibodies in a sequential regime called germline targeting. He says it is vital to redouble efforts to design HIV vaccines specifically to induce neutralizing antibodies. And even in a turbulent environment for research funding, Sanders thinks it’s still viable.

“Absolutely,” he says. “The data that’s coming out of our trials is really reinforcing this.” Sanders and his colleagues just completed an early-phase trial with a vaccine candidate (in part supported by IAVI) and has two other follow-ups planned. “With the current set of studies using germline-targeting immunogens, we have sort of set the rules on how we need to engage those B cells. We’re not shooting in the dark anymore.”

But even as this avenue of HIV vaccine research becomes more certain, the funding is much less so. Though the U.S. case is most dramatic, the administration is not alone in slashing aid abroad: the UK is cutting its foreign aid budget by billions and European research organizations are also hunkering down.

There are also reports that the U.S. National Institutes of Health may be facing wholesale reorganization and slashed budgets. One proposal, as reported in Science,echoing Inside Medicine and the Washington Post, describes 44% cuts for 2026, beginning in October.

“If the NIH is affected in any similar way to USAID, that’s an existential crisis,” says Salim Karim, Director of the Centre for the AIDS Program of Research in South Africa (CAPRISA). “I mean, that would be the end of medical science in the U.S. and its collaborations with countries across the world.” 

It could be much less drastic than this and yet still have a profound effect on scientific research. South African medical historian Rebecca Hodes, who’s written a history of HIV in her home country, sees subtle but constant links between politics and research. “Scientists will craft research agendas in keeping with the funding that is available. It’s not just pure science in searching for particular answers to healthcare questions. Not always,” she says. “Scientists apply for funding and craft their projects in ways that make them more fundable, so that has an impact on clinical research.”

Sanders says the history of HIV shows the influence of funding indirectly: not so much in research agendas or priorities but in how they unfold. “It probably has influenced how quickly certain directions were pursued. I don’t think they decide the direction itself.”

What is more clearly vulnerable to change is the large and delicate infrastructure required to support research and development. International collaborations and partnerships have been a cornerstone of the HIV/AIDS response. The partnerships and networks that were fueling research on HIV/AIDS, malaria, tuberculosis, and many other existing and emerging diseases are one immediate victim of the unprecedented U.S. funding cuts and policy shifts.

“If our science is good enough, we’ll get funded by another funder,” CAPRISA’s Karim says. “But what is really at stake is the nature of what we’ve been trying to do as a global community. We’ve tried to build bridges; to establish collaborations. Even though we are competitors in many respects, we are very good collaborators. We want others to succeed, and we want to help them and be part of their success. This shift in U.S. policy is actually breaking something that we have spent a lot of time building.”

These collaborations, including the ADVANCE program, the BRILLIANT consortium, among many others, were decades in the making. Rebuilding them won’t be easy. “Unfortunately, like any real bridge, it’s very easy to destroy — just drop a bomb on it,” says Karim. “But to rebuild, it will take years.”

Schwartz wholeheartedly agrees. “The personnel who have either been forced out or fired — many of whom have spent decades working in the government and have unique expertise — can’t be replaced with a change of administration or a shift in priorities,” he says.

“Neither can the kinds of programs and partnerships that were established in biomedical research, whether it is the global partnerships through USAID or the broad network that the U.S. is involved in with the global health community. These programs have been a bedrock for decades and they can’t simply be switched back on,” Schwartz adds.

“To see those rebuilt will be the work of many, many years. And even then, it won’t ever look the same as it was. It can’t.”

Michael Dumiak, based in Berlin, reports on global science, public health, and technology.

Suggested further reading:

• US Foreign Aid Freeze and Dissolution of USAID: Timeline of Events (KFF Health News)
• HIV field is reeling after billions in US funding are axed (Science — paywall)
• Getting to the bottom of research funding: Acknowledging the complexity of funding dynamics (Kaare Aagaard et al., PLOS One)