Developing an effective HIV vaccine has long been a challenge due to the rapid mutation rate of the virus, which quickly generates a “swarm” of strains within an individual. However, recent preclinical trials by teams at institutions including Scripps Research, IAVI, the Ragon Institute, and the La Jolla Institute for Immunology have shown promising progress toward an immunization strategy capable of producing rare antibodies effective against a broad array of HIV strains.
These findings, detailed in four papers published across Science, Science Immunology, and Science Translational Medicine on May 16, 2024, build on a 2022 phase I clinical trial by IAVI. The trials focus on stimulating the body to produce broadly neutralizing antibodies (bnAbs), which can block many HIV variants but are rarely produced naturally.
One pivotal strategy discussed involves using a priming immunogen to activate the right precursor B cells, followed by booster immunogens to further mature these cells into potent bnAbs, targeting classes like VRC01 and BG18. The VRC01 class can neutralize over 90% of diverse HIV strains, and BG18 targets sugars on the HIV spike protein.
The collaborative efforts supported by the Scripps Consortium, the Collaboration for AIDS Vaccine Discovery, the Bill & Melinda Gates Foundation, and Moderna have been crucial. For instance, a study using a priming immunogen successfully activated rare BG18 precursors in animal models. This priming was validated through cryo-EM structural analysis, suggesting similar success could be achieved in humans.
Further studies demonstrated the capability to guide these B cells towards bnAb development using sequential immunization strategies. This included new booster immunogens that encourage the immune system to mature these responses.
The culmination of these efforts shows a significant stride in understanding how to activate and guide the maturation of antibody responses against HIV, setting the stage for upcoming experimental medicine trials and potentially paving the way for a viable HIV vaccine.
