Breakthrough HIV vaccine triumphs in phase 1 clinical trial

However, so far, triggering bnAbs through vaccination has been impossible. Therefore, the researchers designed the key particle in the vaccine in such a way as to prepare the body to generate these neutralizing antibodies.

Researchers have been trying for more than 40 years to develop a vaccine for HIV. However, efforts were met with less success due to HIV's tendency to mutate. Excluding a few high-profile cases, no one has been cured of an HIV infection.

The technique can train the body to recognize various strains of HIV

The International AIDS Vaccine Initiative announced the start of this Phase 1 clinical trial in 2018. Overall, 48 participants, aged 18 to 50, received the vaccine candidate or a placebo. Thirty-five out of 36 of those were dosed with the experimental vaccine, and their body showed the activation of the bnAb-precursor B cells, which is the first step toward immunity. 

According to William Schief, a professor in the department of immunology and microbiology at Scripps Research, and one of the study authors, this technique can train the immune system to recognize globally occurring HIV subtypes. 

Schief and team's vaccine will be used in a series of multiple shots, and each will employ a different HIV particle to train the immune system.

According to Business Insider, as the series comes to an end, the engineered molecules get closer to the HIV viruses, until the antibodies generated can bind to various strains of HIV.

"There are 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.

No one reported major side effects. Mild effects like pain at the site of injection or headaches were resolved in a day or two.

The team is currently working with Moderna

Though the results were published Thursday, they were first announced in 2021 at the virtual conference hosted by the International AIDS Society HIV Research for Prevention.

Schief and the team will not be working on the protein-based model used in this study. Instead, they are currently working with Moderna to develop and test a vaccine to deliver the immune-training HIV particles via mRNA.

Phase 2 trials will begin after a while. Schief added that there is no surety the vaccine will be a winner. However, if it does, it could be helpful to make other vaccines too.

"We're optimistic that there are 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."

Study abstract:

Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine–priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.