In the Masiphumele township in Cape Town — which hosts one of the Desmond Tutu Foundation’s vaccine research facilities — 1 in 4 people live with HIV, the virus that causes AIDS.
South Africa has the greatest burden of HIV in the world — of its 60 million people, 8.2 million are living with the deadly disease. Globally, in 2021, around 650,000 died from AIDS-related illnesses.
The Desmond Tutu Foundation was founded by the famous South African cleric to carry out HIV research and find treatments, including a vaccine. The foundation also studies other diseases such as tuberculosis, which is often comorbid with HIV, as well as COVID-19.
Researchers at the foundation hope messenger RNA technology may provide a breakthrough in their search for a vaccine but warn that HIV is more complex than COVID-19.
The search for a vaccine
For more than four decades, scientists have been trying to find an effective vaccine for HIV. Back in 1997, former United States President Bill Clinton predicted that an HIV vaccine would be developed within a decade. Twenty-five years later, scientists still have not developed an HIV vaccine, but research into preventing AIDS has come a long way, significantly reducing mortality caused by the disease, which at its peak in 2004 killed 2 million people in one year.
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Now, if someone who has HIV takes antiretrovirals or ARVs, in most cases, they are able to manage the disease. But there is still a stigma around the illness, meaning that people often do not come forward to take the medication. Others end up forgetting to take it on time, causing many unnecessary deaths.
“We know that the cornerstone for epidemic control of any infectious disease is an effective vaccine,” Dr. Linda-Gail Bekker, CEO of the Desmond Tutu Foundation and former president of the International AIDS Society, told Devex.
“Whilst we have seen terrific progress in antiretroviral therapy and ARV based prevention, there are certain drawbacks to the use of systemic pharmaceutical agents such as side effects, need for adherence, drug-drug interactions to name a few that can be overcome with an effective and affordable vaccine,” she said.
Trialing new HIV treatments
Many HIV vaccine candidates have been developed since the late 1980s, but none have been proven to be effective. There’s only ever been one HIV vaccine trial ever that showed some promise: a Thai study beginning in 2003, where the HIV infection rate for those who received the vaccine was 31% lower than the rate of infection among volunteers who received the placebo. The vaccine would have needed at least a 50% efficacy to have been licensed.
Trials are ongoing at the Masiphumelele center on Lenacapavir, an anti-retroviral drug made by Gilead Sciences that is administered via injection every six months to prevent HIV infection. It follows the development of Cabotegravir, another drug that is taken every two months, which led to an 88% reduction in HIV acquisition for women in sub-Saharan Africa who took part in the trials. Bekker said that having to take Lenacapavir only twice a year would be a “game-changer” in the fight against HIV.
The foundation is also testing an experimental HIV vaccine that uses a chimpanzee virus, in a similar way to the AstraZeneca COVID-19 vaccine, at several sites in South Africa.
Knowing the antigen
Bekker said an HIV vaccine is a tough nut to crack, compared to COVID-19.
“In comparison to SARS-COV-2, the HIV virus is complex, and there's proof to be a formidable foe,” she said. “SARS-COV-2 almost had a spike antigen that was crying out to be turned into a vaccine.”
This month, scientists published a paper that showed that primates developed neutralizing antibodies capable of targeting HIV after they received an experimental vaccine. Often animal models can be a good comparison with humans, but Bekker said that scientists don’t yet fully understand what the animal model for an HIV vaccine should be.
The main challenge is knowing the antigen, the substance that induces the immune response from the body to fight the virus. Vaccines are designed around known antigens of the disease, such as the viral spike protein of COVID-19, to enable the body to generate antibodies to immunize them.
The COVID-19 antigen is “obvious” but HIV is “a master of camouflage,” Bekker said.
“Knowing which is the best part of the pathogen to imitate in a vaccine is the fundamental thing that has to be discovered,” she said, adding that there has also been a lot more investment in COVID-19 vaccines.
“We got gold within nine months. It was extraordinary from beginning to licensure, and here we are, 40 years into the HIV pandemic, we have not seen anywhere near the same kind of investment,” she said.
But there are reasons for renewed optimism. The recent discovery of neutralizing antibodies allows researchers to “open an area of inductive discovery of other vaccines.” In June 2021, the World Health Organization announced the opening of Africa’s first mRNA hub to research and manufacture vaccines using the new technology.
Previously, vaccines stimulated the immune system with an inactivated or weakened version of the virus. mRNA teaches our cells to make proteins that will trigger an immune response to the pathogen.
Bekker said mRNA technology — which has been around for decades but was first certified on a COVID-19 vaccine — will enable a back-engineered approach that will allow scientists to produce new vaccines much more quickly than the older viral vector vaccines. Rather than taking several years, tailoring a vaccine to respond to a new virus or variant can take weeks.
Vaccine trials
Moderna is also working on an HIV candidate. In May, the company and the International AIDS Vaccine Initiative launched phase one trials in the United States, Rwanda, and South Africa that aim to evaluate mRNA HIV vaccine antigen for safety and immunogenicity and strengthen regional scientific capacity. The trials are on healthy humans to see if their bodies generate an immune response to the experimental vaccine.
Brett Leav, an executive director at Moderna, heads up the company’s research for public health vaccines. He was responsible for overseeing the Moderna mRNA COVID-19 vaccine clinical program and is now leading the development of the HIV vaccine.
Speaking about the trials, he told Devex: “These are not efficacy studies. These are what we call immunogenicity and safety trials that are intended to validate a proof of concept in terms of an approach to generate an immune response to the virus. This should be broad and theoretically be able to result in what we call neutralizing antibodies that could theoretically prevent infection of a wide variety of HIV isolates.”
Leav said that if the current trials go according to plan, Moderna will later conduct efficacy trials in people at risk of acquiring HIV.
Moderna is working in Rwanda and South Africa with the primary goal of capacity building “so that for future trials, including efficacy studies, we will have built the infrastructure and established collaborations in those countries to be able to conduct efficacy studies where the product will be very important.”
Though Leav did not comment on the research timeline, he is “cautiously optimistic” that an HIV vaccine can be developed in the next few years.
“The concept we're testing here is actually from some early positive results that we've seen from non-clinical (animal) models that give us reason to believe this approach may offer some chance of success,” he said.
Though there is hope that mRNA technology may make it easier to find an HIV vaccine, Bekker emphasized the need for investment.
“I would not want to say that because we did so well in COVID, it is going to be similar for HIV, because we are dealing with a different pathogen that is complex. But I do think what we can learn from COVID-19 is that with investment and with a lot of incredible attention and focus, we would see a lot more progress than what we have done today,” she said.
About the author
Jack Dutton
Jack Dutton is a freelance correspondent and editor based in Cape Town, South Africa. For seven years, he has reported on topics ranging from politics and development to business and culture. He previously worked in London as digital editor for the United Arab Emirates' The National newspaper, where he covered major global stories including the COVID-19 pandemic, Brexit talks, and the 2020 U.S. election. Prior to that, he was an editor at Euromoney, covering the aviation sector for Airfinance Journal magazine. His freelance writing has appeared on Al-Jazeera, Newsweek, the Guardian, The Independent, The Psychologist, and more.
