What’s Next for the World’s First HIV Vaccine?

When the world needed a COVID vaccine, leading HIV investigators answered the call to intervene in the coronavirus pandemic. Now, efforts to discover the world’s first HIV vaccine are revitalized.
“The body is capable of making antibodies to protect us from HIV,” says Yunda Huang, PhD, from the Fred Hutchinson Cancer Center in Seattle, Washington, who sat down with me before her talk today at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting.
Huang spoke about the path forward for neutralizing antibody protection after the last attempt in a generation of HIV vaccine development ended in disappointment.
The past two decades marked the rise in HIV broadly neutralizing antibodies, with vaccine strategies to induce them. Promising advances include germline approaches, mRNA, and nanoparticle technologies.
The PrEP vaccine trial testing two experimental prevention regimens in Africa was stopped after investigators reported there is “little to no chance” the trial will show the vaccines are effective.
A Shape-Shifting Virus
HIV has been called the shape-shifting virus because it disguises itself so that even when people are able to make antibodies to it, the virus changes to escape.
But Huang and others are optimistic that an effective vaccine is still possible.
“We cannot and will not lose hope that the world will have an effective HIV vaccine that is accessible by all who need it, anywhere,” International AIDS Society (IAS) Executive Director Birgit Poniatowski said in a statement in December, when the trial was stopped.
HIV is a still persistent problem in the United States, according to the Centers for Disease Control and Prevention that reports it has affected an estimated 1.2 million people.
With new people infected every day around the globe, Dr Huang says she feels a sense of urgency to help. “I think about all the people around the globe and the large number of young girls being hurt and I know our big pool of talent can intervene to change what we see happening.” 
Huang says the clinical trial failures we’ve seen so far will help guide next steps in HIV research as much as successes typically do.
Advances in the Field
With significant advances in protein nanoparticle science, mRNA technology, adjuvant development, and B-cell and antibody analyses, a new wave of clinical trials are on the way.
And with so many new approaches in the works, the HIV Vaccine Trials Network is retooling how it operates to navigate a burgeoning field and identify the most promising regimens.
A new Discovery Medicine Program will help the network assess new vaccine candidates. It will also aim to rule out others earlier on.
For COVID-19 and the flu, multimeric nanoparticles are an important alternative under investigation that could also be adapted for HIV.
Huang says she is particularly excited to watch the progress in cocktails of combination monoclonals. “I’ve been working in this field for 20 years now and there is a misconception that with pre-exposure prophylaxis, our job is done, but HIV is so far from away from being solved.”
But you just never know, Huang says. With new research, “we could bump on something at any point that changes everything.”
 
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