An HIV vaccine candidate is showing positive early results, prompting a critical component of the human immune response in 97 percent of vaccine recipients. It was a small, phase 1 trial testing a vaccine that was made out of an engineered version of a protein that exists on the HIV virus. This particle was designed to get the body ready to generate broadly neutralizing antibodies, which are thought to be critical to create immunity against HIV. Broadly neutralizing antibodies would recognize a large swath of HIV subtypes, which is necessary to provide immunity because the HIV virus mutates frequently. Forty-eight participants either received the vaccine candidate or a placebo, and 35 out of 36 of those dosed with the vaccine candidate showed activation of broadly neutralizing antibody precursor B cells that could produce the first step on the way to immunity. The crux of this technique is essentially to train the immune system to recognize a wide array of naturally occurring HIV subtypes, according to William Schief, one of the authors of the study. Schief is a professor in the department of immunology and microbiology at Scripps Research. "There's only a few patches on the surface of the HIV spike that remain the same or relatively the same across different isolates. And we're trying to elicit very specific antibodies that have very specific properties that allow them to bind to those exact patches," Schief said. In the phase 1 study, no one reported serious side effects, and other side effects like pain at the injection site or headaches were mild to moderate, and they resolved in one to two days. These results, published in the academic journal Science on December 1st, 2022, which was World AIDS Day, were first announced in 2021 at the virtual conference hosted by the International AIDS Society HIV Research for Prevention. The trial was co-run by the International AIDS Vaccine Initiative and Scripps Research. Researchers have been trying to create an HIV vaccine for nearly 40 years HIV is notoriously difficult to vaccinate against. Part of this is because of HIV's tendency to mutate. By evolving and changing quickly, it can avoid the immune system by making itself harder to recognize. Additionally, virtually no one, short of a few high-profile cases, has been cured of an HIV infection. That means we don't know what sorts of immune cells in the body can actually protect against infection. Theoretically, this vaccine will be the first in a series of multiple shots, each using a different HIV particle to train the immune system. As the shots progress, the molecules get closer and closer to that of the actual HIV viruses, until antibodies produced can bind to many different kinds of HIV. "That's sort of a whole new way of thinking about how to make a vaccine," Schief said. Moderna is developing its HIV vaccine based on similar research According to Schief, his team is currently working with biotech giant Moderna to develop and test a vaccine to deliver the immune-training HIV particles via mRNA, instead of the protein-based model this most recent study used. One phase 1 study is currently testing the same particle, as well as another engineered particle, with an mRNA delivery system. Another study is testing the same particle in a clinical trial in Africa. It will take time before phase 2 trials can begin, according to Schief, and there's no guarantee that the vaccine will ultimately work. But if it does, this technique could be used to make other vaccines, he said, like a universal coronavirus or flu vaccine. "We're optimistic that there's some chances that this approach may be helpful for more than just HIV," said Schief, "even though if it only helps HIV that would be enormous." Source
