SA launches first human HIV vaccine trial

A safe, affordable vaccine taken in the first year of life — and never again.

That is the long-term prize scientists are chasing as South Africa launches its first-ever human HIV vaccine trial, a milestone moment in a decades-long global race to end the epidemic.

A group of about 20 HIV-negative South Africans has become the first in the country to participate in a new HIV vaccine trial that researchers hope could lay the groundwork for a future generation free of the virus.

The BRILLIANT 011, a first-in-human clinical trial, was officially launched at the Desmond Tutu HIV Foundation (DTHF) research site at Groote Schuur Hospital in Cape Town.

South Africa remains the epicentre of the global HIV epidemic, with an estimated 8.15-million people living with HIV, about 6.3-million of whom are on treatment.

The trial is conducted by the South African Medical Research Council (SAMRC), the DTHF and the Wits Health Consortium and forms part of the BRILLIANT Consortium (BRinging Innovation to cLinical and Laboratory research to end HIV In Africa through New vaccine Technology).

In 2023 the consortium was awarded R867m in funding from the US to implement the HIV Vaccine Innovation, Science and Technology Acceleration in Africa (HIV-Vista) programme.

Prof Glenda Gray, SAMRC chief scientific officer and a distinguished professor at Wits University’s faculty of health sciences, said the trial marks a critical early step in HIV vaccine development.

“We do not have an HIV vaccine at the moment,” she said. “That is why these early-phase trials are so important.”

Gray said participants were recruited through extensive community engagement. “We spent a lot of time with potential participants to see if they were ready. This is not a simple decision.”

All participants had to be healthy and HIV-negative, she said. “We also did not want people who are at high risk of acquiring HIV, as that would confuse our analysis. At this stage the aim is to see how the vaccine works on the immune system.”

As part of the study, researchers collect large volumes of blood and perform leukapheresis — a process that removes white blood cells — to closely study how the immune system responds to the vaccine.

Gray said the BRILLIANT 011 trial is unique because it was designed by African scientists, using vaccine products that were first identified in African trial participants and later further developed in the US.

The trial is run by African investigators, which provides a unique opportunity to strengthen vaccine research and development capacity on the continent.

—  Prof Glenda Gray, SAMRC chief scientific officer

“The trial is run by African investigators, which provides a unique opportunity to strengthen vaccine research and development capacity on the continent,” she said.

Unlike traditional vaccine studies, BRILLIANT 011 uses a cocktail approach, administering two vaccine products together to stimulate strong immune responses. “It also uses a new adjuvant [a drug or other substance to stimulate a strong immune response to the vaccine] that has never been tested with this combination of immunogens,” Gray said.

South Africa already runs one of the world’s largest pre-exposure prophylaxis (PrEP) programmes, with more than 1.3-million participants.

In June last year, a six-monthly injectable HIV prevention drug, lenacapavir, was approved by the US Food and Drug Administration. South Africa is among the first countries expected to receive doses of the long-acting medication, which is also used in HIV treatment.

Prof Nigel Garrett, chief scientific officer at the DTHF, said the country was preparing for an ambitious PrEP rollout using lenacapavir. “This is an exciting time to work in HIV prevention research and policy because there is a real chance to make an impact on the epidemic,” Garrett said. “However, history has taught us that the most sustainable and powerful tools to control infectious diseases are vaccines.”

He stressed that while other prevention options expand, HIV vaccine research must continue.

Garrett said vaccine safety was the first and non-negotiable measure of success. “Beyond that, success in this trial would be if we can show that the vaccines trigger precursors of broadly neutralising antibodies. These are the super-strong antibodies capable of blocking many forms of HIV. If we can demonstrate this pathway, it would move the entire HIV vaccine field forward.”

Such findings would allow scientists to design the next phase of trials, testing vaccine regimens in larger populations, with the aim of controlling the epidemic within the next decade. Participants will remain in the study for 12 months and have been encouraged to adhere strictly to study procedures until completion.

Garrett said the persistence of the BRILLIANT Consortium reflects South Africa’s continued leadership in HIV research. “It stands as a powerful example of our commitment to innovation, partnership and scientific excellence,” he said.

Prof Penny Moore, a leading immunologist, said the trial was only possible because of unprecedented international collaboration. “It will not only advance HIV vaccine design on the continent but also massively increase immunology expertise in South Africa, preparing us for future pathogens and outbreaks,” she said.