Novel Vaccine Approach for HIV Prevention Shows Promising Results in First-in-Human Trial

Investigators believe that an effective HIV vaccine would need to produce broadly neutralizing antibodies that would work on different strains of the virus.

A phase 1 trial of a novel approach for HIV vaccination successfully stimulated production of rare immune cells needed to start the process of generating antibodies against the virus. Notably, the targeted response was detected in 97% of participants who received the vaccine, according to a press release.

“This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens, as well,” said William Schief, PhD, whose laboratory developed the vaccine, in a press release. “With our many collaborators on the study team, we showed that vaccines can be designed to stimulate rare immune cells with specific properties, and this targeted stimulation can be very efficient in humans. We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens.”

HIV affects more than 38 million people globally and is known to be one of the most difficult viruses to target with a vaccine. One of the major challenges is because the virus constantly evolves into different strains to evade the immune system.

Investigators have worked for decades to create a vaccine that would stimulate the immune system to create rare but powerful antibodies called broadly neutralizing antibodies (bnAbs). According to the press release, bnAbs are specialized blood proteins that could attach to HIV spikes and disable them via important yet difficult-to-access regions that don’t vary much from strain to strain.

“We and others postulated many years ago that in order to induce bnAbs, you must start the process by triggering the right B cells—cells that have special properties giving them potential to develop into bnAb-secreting cells,” Schief explained in the press release. “In this trial, the targeted cells were only about 1 in a million of all naïve B cells. To get the right antibody response, we first need to prime the right B cells. The data from this trial affirms the ability of the vaccine immunogen to do this.”

The strategy of targeting naïve B cells with specific properties is called germline-targeting, because these young B cells display germline genes. Investigators believe the approach could also be applied to vaccines for other challenging pathogens, such as influenza, dengue, Zika, hepatitis C virus, and malaria.

The clinical trial, IAVI G001, enrolled 48 healthy adult volunteers who received either a placebo or 2 doses of the vaccine compound along with an adjuvant developed by GSK. According to the investigators, the novel design, the clinical trial, and the molecular B cell analyses provide a roadmap for further progress in an HIV vaccine.

“This is a tremendous achievement for vaccine science as a whole,” said Dennis Burton, PhD, scientific director of the IAVI Neutralizing Antibody Center and director of the NIH Consortium for HIV/AIDS Vaccine Development, in a press release. “This clinical trial has shown that we can drive immune responses in predictable ways to make new and better vaccines, and not just for HIV. We believe this type of vaccine engineering can be applied more broadly, bringing about a new day in vaccinology.”

REFERENCE

First-in-human clinical trial confirms novel HIV vaccine approach developed by IAVI and Scripps Research [news release]. Scripps Research; February 3, 2021. https://www.scripps.edu/news-and-events/press-room/2021/20210203-hiv-vaccine.html. Accessed February 9, 2021.