No virus has proved more evasive. Hundreds of HIV vaccines have entered testing; none has succeeded at providing durable protection against infection. And the need remains vast: In 2025, roughly 1.2 million new HIV infections<\/a> were reported; anti-retroviral treatments have turned it into more of a survivable disease, but more than half a million people died from AIDS-related causes the same year. There is still no known cure.<\/p>\n So researchers like Bekker, an infectious disease specialist at the University of Cape Town, have more hope now, in part because there is finally a clearer idea of what an effective vaccine needs to do. It must coax the immune system into producing a particular type of protective antibody, a rare class of defender, capable of recognizing and disabling HIV despite the virus\u2019s extraordinary diversity and rapid ability to mutate.<\/p>\n No one yet knows how to reliably do that. But mRNA is uniquely suited to the task of finding out, vaccinologists say. Thanks to the platform\u2019s speed and flexibility<\/a>, researchers can iterate rapidly through the otherwise laborious process of designing, testing, and refining the series of vaccine components needed to guide the body toward making those essential antibodies.<\/p>\n A nurse preparers a trial dose of PrepVacc to inject into a participant in 2022 in Masaka, Uganda, as part of an African-led HIV prevention trial. Luke Dray\/Getty Images<\/p>\n At the start of last year, Bekker and her colleagues were ready to put that strategy to the test. The clinical trial for their new mRNA-based HIV vaccine was just on the verge of enrolling its first participants. But the project depended on the same backing that had sustained HIV vaccine research for decades: US government funding. Washington had long supplied roughly 90 percent of the world\u2019s investment in the field<\/a>. Then President Donald Trump returned to office.<\/p>\n Within hours of his inauguration, Trump signed an executive order freezing foreign aid<\/a>. The $45 million contract from the US Agency for International Development (USAID) that was supposed to fund clinical trials like Bekker\u2019s disappeared, as did a web of other funds, many routed through the National Institutes of Health (NIH), that had helped fuel the field\u2019s progress for years.<\/p>\n The timing could hardly be more cruel. After 40-odd years of chasing a shape-shifting foe, scientists believe they now know what kind of immune response an HIV vaccine must generate \u2014 and have in mRNA a powerful new tool for pursuing it. But just as many researchers have finally glimpsed a path to victory, the United States and much of the funding has pulled away from the fight.<\/p>\n From the outset, the target for preventing HIV was clear. Within a year of identifying the virus as the cause of AIDS in 1983, researchers had zeroed in on its envelope protein<\/a> as the most promising point of attack for a vaccine.<\/p>\n Protruding from the virus\u2019s surface in knobby clusters, the envelope protein acts like a molecular grappling hook, latching onto immune cells before pulling the virus itself inside. Without this feature, HIV cannot infect a cell.<\/p>\n Much as the coronavirus spike protein would later become the basis for Covid vaccines, this protein on the surface of HIV seemed an obvious bullseye. But identifying the target didn\u2019t mean researchers could hit it. Most of what the immune system sees of the envelope protein is actually just a decoy. The parts that stick out and draw the strongest immune response are also its most changeable, differing from one strain to the next and mutating freely whenever antibodies close in, leaving the body to waste its firepower on a target that keeps slipping away.<\/p>\n Candidate vaccines kept making the same mistake. They would elicit plenty of antibodies, but not the kind that could keep up with the virus. Time and again, promising candidate vaccines generated excitement in the laboratory, only to come up empty<\/a> when it mattered most in large-scale clinical testing.<\/p>\n The field\u2019s fortunes started to change in the late 2000s when researchers began studying the small fraction of people living with HIV who developed antibodies capable of recognizing the virus\u2019s concealed, conserved features. Though these hard-won antibodies came too late to protect their makers, they gave scientists a molecular blueprint for the defenses a vaccine would need to build.<\/p>\n As the field came to learn, these \u201cbroadly neutralizing antibodies<\/a>\u201d do not appear overnight but rather after years of battle with the virus.<\/p>\n The challenge, then, was to design a vaccine that would not just trigger an immune response but guide a person\u2019s immune system through the same evolutionary journey. This would require a succession of vaccine components to prompt a carefully choreographed process within the body, rather than the single, fixed target that suffices for shots against measles or hepatitis B.<\/p>\n A researcher dilutes mRNA at a lab in Orleans, France. Researchers are working to develop new treatments for numerous diseases using messenger RNA, which became widely known to the public through the vaccines developed against Covid. Jean-Francois Monier\/AFP\/Getty Images<\/p>\n It was a strategy rooted in rational design but dependent on trial and error. Progress would come through a steady stream of small proof-of-concept studies, each informing the next generation of vaccine candidates. Ordinarily, it would take at least a year \u2014 often longer \u2014 to manufacture and prepare each vaccine iteration before it could be tested in people.<\/p>\n But then the Covid pandemic rocketed mRNA into the spotlight.<\/p>\n mRNA technology upends the old recipe of vaccine development. Conventional shots work by showing the immune system a mugshot of the enemy: a killed or weakened germ, or one of its proteins, grown batch by batch in vats of cells or eggs. An mRNA vaccine takes a different route. Rather than supplying the mugshot, it supplies the instructions to draw one: a short, lab-printed strip of messenger RNA, the molecule cells normally use to ferry genetic directions from DNA to their protein-making machinery.<\/p>\n Inject the right sequence, and it will program the body\u2019s own cells to become tiny factories, producing the target protein and presenting it to the immune system as if it were the real intruder. Because it is all just code, refining a design means editing text, not rebuilding a factory \u2014 the work of days, not months.<\/p>\n \u201cWe\u2019ve been able to design vaccines in real time,\u201d says University of Pennsylvania Perelman School of Medicine assistant professor Ted Kreider, who is a specialist in infectious diseases.<\/p>\n To HIV researchers, the appeal was obvious. HIV\u2019s greatest weapon was its ability to shift and adapt. Now, at last, a vaccine could, too.<\/p>\n The timing was ideal. Just as researchers were beginning to map the path to an effective vaccine, mRNA offered a way to move down that path at speed. With vaccine designs no longer bottlenecked by design and manufacturing, what once might have taken decades of stepwise vaccine development could, thanks to mRNA, be compressed into years.<\/p>\n Across a growing number of clinical trials, researchers are now testing different vaccine components, different sequences, and different delivery platforms, searching for the combination that most effectively nudges the immune system toward a truly HIV-thwarting response.<\/p>\n A paper published last month in Nature offered one such path forward, showing in monkeys that a painstaking sequence of eight shots could coax the immune system<\/a> into producing potent antibodies capable of neutralizing a broad range of HIV strains. But even the study\u2019s authors see a catch. \u201cIt\u2019s still too many [shots] to be practical in humans,\u201d says Dennis Burton, a professor of immunology and microbiology at Scripps Research who worked on the project.<\/p>\n Whether mRNA ultimately becomes the vaccine itself \u2014 or simply the tool that helps researchers discover it \u2014 remains an open question.<\/p>\n The fundamental challenge for now, after all, is vaccine design, notes Mark Feinberg, president and CEO of IAVI, a nonprofit research organization focused on developing vaccines against HIV. And for that task, he says, \u201cthe most obvious advantage of mRNA is simply the speed of getting an idea from the laboratory to the clinic.\u201d<\/p>\n But if the technology reaches the finish line, researchers say it could offer other advantages as well. Because the protein is made inside the body\u2019s own cells rather than in a lab, it folds and displays itself much as it would on the real virus, giving the immune system a more faithful target to train against. That way, when the real virus arrives, the body already knows its true face.<\/p>\n It also gives vaccine designers an unusual number of knobs to turn, notes Kristie Bloom, an mRNA vaccine researcher and molecular biologist at the University of Witwatersrand in South Africa. By altering the vaccine\u2019s formulation, dose, or genetic design, researchers can shape not just the magnitude of the immune response but also its balance: favoring antibody-producing B cells, virus-killing T cells or some mix of the two.<\/p>\n With mRNA, \u201cthere\u2019s quite a bit of flexibility,\u201d she says.<\/p>\n For all the putative upsides, however, mRNA does carry some baggage. There are concerns about public acceptance<\/a> given the intense backlash and misinformation campaigns<\/a> that followed the rollout of Covid-19 vaccines. And though those shots ultimately proved remarkably safe, with very low rates of serious side effects, a peculiar skin problem has emerged in early-stage trials of mRNA vaccine candidates for HIV specifically.<\/p>\n In two<\/a> separate trials<\/a> reported last year, around 1 in 12 participants who received mRNA-based HIV vaccines manufactured by Moderna developed chronic urticaria, a form of persistent hives that in some cases endured for years. The vaccines encoded different portions of HIV\u2019s envelope protein, yet both produced the same unexpected side effect.<\/p>\n The fact that the reactions appeared across distinct vaccine designs \u2014 but never before in Moderna\u2019s other mRNA vaccine programs \u2014 has fueled suspicion that something about HIV\u2019s envelope protein itself may be involved. Even so, no clear explanation has emerged<\/a>.<\/p>\n \u201cWe\u2019ve ruled a bunch of things out,\u201d notes William Schief, a professor at Scripps Research\u2019s department of immunology and microbiology who doubles as vice president for protein design at Moderna, \u201cbut there\u2019s no smoking gun.\u201d<\/p>\n Schief is continuing to investigate the source of the immune reactions. But not wanting an unresolved safety signal to bring the program to a halt, he and his collaborators have pressed ahead with lower-dose versions of the vaccine, betting that the hives will fade while the desired immune response remains intact.<\/p>\n That strategy is now being evaluated in an IAVI-backed trial led by Bekker in South Africa. Known as IAVI G004<\/a>, it has yielded encouraging early results. (Unlike the African-developed vaccine whose launch was derailed by the USAID funding freeze, this study is testing a different mRNA vaccine candidate, manufactured by Moderna.)<\/p>\n At the lowest dose tested, just one-tenth of the amount used in the original studies, the hives that had troubled earlier trials never materialized, says Bekker. Her team has since moved on to a somewhat higher dose, seeking the sweet spot between safety and immune potency.<\/p>\n All of these discoveries and challenges along the way have helped map a path forward. \u201cWe know what we need to do,\u201d says Barton Haynes, director of the Human Vaccine Institute at the Duke University School of Medicine. The task for them now is to move through the necessary iterations as quickly as the science \u2014 and the funding and political landscape \u2014 allow.<\/p>\n When Bekker and her team learned about the sudden funding cut that would halt their African-designed, USAID-funded vaccine study in January 2025, they were already in Tanzania to prepare its launch. They immediately had to stop work on the project, which had been years in the making. \u201cIt was like falling into a black hole of depression,\u201d she says.<\/p>\n And the setbacks kept coming<\/a>. With prominent vaccine critic Robert F. Kennedy Jr. overseeing US health policy, the federal government moved to undermine both vaccine science broadly and mRNA technology in particular.<\/p>\n The NIH, in addition to terminating dozens of smaller HIV-related grants, began winding down<\/a> its flagship Consortia for HIV\/AIDS Vaccine Development (CHAVD) program, which has long served as a cornerstone of global HIV vaccine research, while other federal agencies curtailed support for mRNA vaccine projects<\/a> across multiple disease areas.<\/p>\n At the same time, South Africa, the continent\u2019s leading center for biomedical research, found itself in the Trump administration\u2019s crosshairs over allegations of anti-white discrimination<\/a>. New federal research grants were no longer permitted to support collaborations with South African scientists, severing ties that had underpinned years of international HIV research.<\/p>\n \u201cThat\u2019s a perfect storm to prevent us from building on the most exciting science HIV vaccines have had in 45 years,\u201d says Mitchell Warren, executive director of AVAC, a nonprofit dedicated to HIV prevention access and policy.<\/p>\n Yet for all the financial and political disruption, the scientific momentum hasn\u2019t stopped. Philanthropic organizations and governments elsewhere have stepped up to help fill the funding gap, allowing key trials to move forward, although in scaled-down forms with more modest ambitions.<\/p>\n The Africa-led effort that Bekker had dreamed of was salvaged, with emergency backing<\/a> from the South African Medical Research Council, albeit in diminished form and built, in the end, on the same protein-based technology that mRNA was meant to leapfrog.<\/p>\n The only mRNA-based HIV vaccine study that is actually underway in Africa is IAVI G004: a program designed by US scientists, not by locals, and funded largely by the Gates Foundation.<\/p>\n A longtime backer of HIV research, that foundation is estimated to invest around $70 million annually \u2014 with $64 million being invested in 2022, and $70 million in 2026 \u2014 across a global portfolio of HIV vaccine programs. That\u2019s a substantial sum, though only a fraction of the hundreds of millions of dollars once provided by the NIH, USAID, and other federal agencies.<\/p>\n For now, some of that funding continues to flow. But even what remains is far from assured. The Trump administration\u2019s proposed 2026 budget would slash the National Institute of Allergy and Infectious Diseases \u2014 the NIH institute that has long anchored HIV vaccine science<\/a> \u2014 along with the Office of AIDS Research<\/a> that coordinates HIV research across the entire NIH, leaving the field\u2019s longer-term future in doubt.<\/p>\n \u201cWe\u2019re not going to be able to fill the gap that\u2019s been left by the US government,\u201d acknowledges Nina Russell, director of TB & HIV research and development at the Gates Foundation. Still, she says, the foundation remains determined to keep the most promising vaccine programs moving forward: \u201cWe are super committed to it.\u201d<\/p>\n All of these changes have left the research field daunted, but not hopeless. \u201cIt\u2019s been a very disruptive time,\u201d acknowledges Burton, who leads one of the CHAVD research hubs. But he remains convinced the field is on the right track. \u201cThe pieces of the puzzle are in place,\u201d he says. \u201cIt\u2019s obviously been a long, long journey, but you can begin to see the end.\u201d<\/p>\n The funding crisis and political challenges are not the only forces reshaping HIV vaccine development.<\/p>\n For much of the HIV epidemic, which has killed over 40 million people worldwide<\/a>, even a partially effective vaccine might have been enough to transform the course of HIV. Today, however, vaccine researchers are also competing against long-acting preventive drugs<\/a> that can protect people for months at a time with just two injections.<\/p>\n These drugs are an enormous step forward for HIV protection, but they also raise the standard the vaccine field must meet, notes Warren. \u201cThe bar for a licensed vaccine that is going to have a public health impact has gotten much higher,\u201d he says.<\/p>\n But these prophylactic drugs, which began as daily pills and have evolved into long-acting injectables, are only as good as the systems that deliver them. Cost, stigma, and the need for regular clinic visits have limited access in many countries with the highest HIV burdens<\/a>. A vaccine, by contrast, that provided years of protection after a handful of doses could overcome many of those barriers.<\/p>\n That is precisely why many scientists view the current retreat of the US government with such alarm<\/a>. After decades of disappointments and billions of dollars in investment, the field finally believes it has a coherent strategy for building an effective HIV vaccine. The fear is that momentum could stall<\/a> just as researchers have begun to see a path across the finish line. As a result, what once seemed like a scientific problem increasingly looks like a political one.<\/p>\n![\"A](\"https:\/\/www.newsbeep.com\/il\/wp-content\/uploads\/2026\/07\/gettyimages-1386008123.jpg\"\/)
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