US funding cuts imperil African search for HIV vaccine

12 Mar 2025

A groundbreaking project to study potential HIV vaccines in several African countries has been derailed by an abrupt cut in funding from the US government. As a result, several promising vaccine candidates might not be tested in clinical trials.

A group of leading African researchers trying to develop effective vaccines against HIV is trying to figure out how to salvage their ambitious research after losing funding due to the Trump administration’s cuts to foreign aid.

The group, called the BRILLIANT Consortium, led by the South African Medical Research Council (SAMRC), comprises researchers from eight African countries, many of whom have already played a key role in advancing the world’s understanding of HIV science, as their research has shaped how HIV is treated and prevented. They have also been deeply involved in decades-long efforts to develop an effective HIV vaccine.

While antiretroviral treatment is highly effective and keeps people who are living with HIV healthy, it is not a cure and the treatment has to be taken for life. The development of an effective HIV vaccine or cure thus remains vital to ending the epidemic – particularly as HIV programmes around the world now face extreme financial strain in light of US aid cuts.

Vaccines that induce bNAbs

While three decades of research has failed to deliver an effective vaccine against HIV, these efforts have built a vast body of knowledge about how the virus evades the immune system. The key problem, it turns out, is HIV’s broad genetic diversity and how fast it mutates. In short, the virus shape-shifts too much and comes in too many variants for traditional vaccines to target it successfully.

As a result, a consensus has emerged among researchers that to be effective, an HIV vaccine must be able to induce broadly neutralising antibodies (bNAbs). The “broadly” refers to the ability of these types of antibodies to neutralise many strains of HIV. With the right bNAbs it is hoped that HIV won’t be able to mutate its way out of trouble.

Broadly neutralising antibodies were discovered in the days before antiretroviral therapy was widely accessible. At the time, scientists found that a small number of people living with HIV were able to remain healthy without taking antiretrovirals (ARVs). Some of them naturally developed bNAbs that prevented the progression of HIV in their bodies and allowed them to stay healthy without treatment. Scientists are now hoping to elicit this kind of bNAb immune response using vaccines.

An abrupt halt

With an ambitious set of studies in the pipeline, the BRILLIANT Consortium is at the cutting edge of developing and testing these new approaches to HIV vaccine development. But abrupt funding cuts mean the future of the project is now highly uncertain.

They were instructed to suspend all work after the Trump administration froze US foreign aid on 20 January and, along with other recipients of USAID funding, received official notice that their grant was terminated on 26 February.

The impact has been immediate and severe.

One vaccine candidate was scheduled to enter phase one clinical trials at the end of January 2025, while two more were on the path to enter clinical trials by early next year. All of these trials are now on hold.

“I can’t think of any other illness where in the middle of groundbreaking research, we’ve just suddenly dropped what we’re doing and abandoned the effort altogether,” Dr Nivashnee Naicker, head of HIV vaccine research at the Centre for the Aids Programme of Research in South Africa (Caprisa), told Spotlight.

The consortium is now trying to secure alternative sources of funding to salvage its most promising and advanced research. It has put out a call for support from African governments, philanthropies and private-sector groups.

The harm caused by the sudden funding cuts is “unquantifiable”, according to Wits University’s Professor Penny Moore. She says the impact extends beyond HIV vaccine development efforts and also affects the indirect benefits that spending on HIV research and infrastructure has in enabling the continent to effectively respond to other infectious disease threats.

‘A trial a year’

The BRILLIANT Consortium aims to advance a number of vaccine candidates from pre-clinical studies to clinical trials, while also identifying new vaccine candidates. (Clinical research involves research that is conducted in humans, after pre-clinical research has been undertaken in labs and animals. Candidate vaccines typically undergo years, and sometimes even decades, of pre-clinical research before they are tested in humans.)

The trial that was supposed to start in January would have been the consortium’s first clinical trial. Called BRILLIANT 001, it was to be followed by two more trials – BRILLIANT 002 and BRILLIANT 003 – all testing HIV vaccine candidates.

“We said we would do at least one clinical trial a year [and] people were like: ‘You’ll never do that, that’s crazy’,” said Professor Linda-Gail Bekker, director of the Desmond Tutu HIV Centre and a co-principal investigator for the BRILLIANT Consortium. “[B]ut after our first year, our scientific advisory group, who are really opinion-leading HIV vaccinologists from around the world, were like: ‘Your progress is eye popping!’”

The pipeline of vaccine candidates under development by the BRILLIANT Consortium largely consists of different immunogens designed to trigger a bNAb response. But it is also developing immunogens to trigger T-cell responses, with the aim to combine immunogens that can elicit both bNAb and T-cell responses into a single vaccine product.

“As a sort of second line of defence, most people acknowledge that you probably also need a vaccine that is going to induce a T-cell response,” said the University of Cape Town’s Professor Wendy Burgess. “So, we had a component [of the consortium] designing a T-cell vaccine. We have learned from 25 years of HIV research… that this is what we need to put together,” she said, explaining that “T-cells do a lot of things in the immune response and T-cells also help the development of antibodies”.

Combining bNAb lineages

The novel idea with BRILLIANT 001 was to elicit a bNAb response by combining two different immunogens into a single vaccine, together with an adjuvant to enhance the immune response.

“We were proposing a strategy that no one had looked at before and this was to put both products together at the same time to see whether we could induce two different lineages of broadly neutralising antibodies,” said Professor Glenda Gray, director of the consortium.

The immunogens in BRILLIANT 001’s candidate vaccine were developed in Europe and the US and donated to the consortium.

When the stop-work orders came through, the consortium had spent a year preparing for the trial and was ready to start administering the first vaccine doses to participants.

“We were working non-stop” to prepare for the trial, said Naicker, who leads the Caprisa eThekwini clinical research site, which is one of the four trial sites. “We received our ethics approval in December… [and] we had completed all of our site activation items.”

The consortium is now racing against the clock to secure funding from alternative sources to allow BRILLIANT 001 to progress before vaccine stock expires.

“If our last participant doesn’t get their first vaccination by about July of this year, then we won’t be able to complete that person’s vaccination, because the vaccine has an expiry date of the following year,” Gray said.

In a bid to save BRILLIANT 001, Bekker said the trial is being redesigned to reduce costs. This means the trial is likely to have fewer participants, take place in fewer countries and investigate fewer endpoints. “We have paired it down to its absolute minimum” to answer the question “do these immunogens make neutralising antibodies?” she said.

Other vaccine candidates at stake

The consortium has several other vaccine candidates in its pipeline at different stages of development. It was hoped that two other candidate products would move into early-stage clinical trials by early next year, said Bekker.

She said the consortium was in discussions with Duke University in the US, as well as biopharmaceutical company Gennova Bio, headquartered in India, to manufacture vaccines for the BRILLIANT 002 and BRILLIANT 003 trials.

In addition, pre-clinical research on vaccine candidates is under way, with messenger ribonucleic acid (mRNA) vaccines produced by the Wits/SAMRC Antiviral Gene Therapy Research Unit (AGTRU). Messenger RNA technology was critical to the development of SARS-CoV-2 vaccines made by Moderna and Pfizer/BioNTech.

AGTRU’s director, Professor Patrick Arbuthnot, said the unit is developing mRNA vaccine candidates based on the genetic sequences of the HIV that infected people who later developed bNAbs.

“The thinking was that we could use the genetic sequences of the HIV that infected these individuals… as the vaccine immunogens to induce the same broadly neutralising antibodies that these patients have,” he explained.

By using an mRNA vaccine platform to make the vaccines they “can tweak the vaccine composition very quickly… change it according to what the results show and what we think might improve the efficacy”.

A number of vaccine candidates have already been identified from people who produced bNAbs following HIV infection.

“Over the last 20 years we’ve identified at least 10 individuals in South Africa who develop broadly neutralising antibodies and we have vaccine candidates based on several of those already that are in early stages in the lab,” Moore said. “At least two of those candidates have already moved into pre-clinical studies, so we have a rich pipeline of ideas that have come through, all of which are halted for now.”

One of the candidates, according to Bekker, which is already in pre-clinical studies and was slated to enter human trials by early next year, is known as CAP256. This immunogen is named after a study participant identified in a Caprisa research cohort was able to naturally develop bNAbs.

Research on the CAP256 immunogen has been under way for 20 years, Moore said. “We are finally at the stage where we had an mRNA version of the vaccine, and it had gone into rabbits and looks really, really promising.” But this research had now “hit… a roadblock” due to the termination of funding.

In addition to testing promising immunogens already in the pipeline, the consortium aimed to identify new potential immunogens by strengthening surveillance of breakthrough infections that occur during clinical trials.

“When someone gets infected on a clinical trial of an HIV vaccine, it’s called a breakthrough infection and then those viruses get sequenced,” Burgess said, adding: “What we wanted to do was come up with updated viral sequences for the viruses that are circulating in our region now.”

Building capacity in African countries

African researchers have long contributed to basic science research and clinical trials for HIV vaccines, but critical gaps remain in the continent’s capacity to develop a new vaccine from concept to delivery. These gaps include analysing trial results and to manufacture clinical grade mRNA vaccines. Clinical-grade products are those that can be tested and used in people. The consortium was hoping to close these gaps.

“The whole point of this grant was to set up the capacity to do everything – from the pre-clinical development, to small-scale manufacture of vaccines, to the clinical lots, to safety and toxicity testing, through to discovery trials, and then measuring the outputs of those discovery trials,” Moore said. This is something “we have to do as a continent [not just] for HIV, but for every other pathogen that’s coming our way”.

“I don’t think it is possible to quantify the damage if we don’t manage to get this pipeline refunded somehow. It certainly goes way beyond HIV.” DM

This article was first published by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.

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