HIV vaccine candidate triggers rare protective antibodies in primates

Researchers from the La Jolla Institute for Immunology (LJI), Scripps Research, and the International AIDS Vaccine Initiative (IAVI) have reported significant progress in the development of an HIV vaccine. Published in Nature, the study details a 14-year collaboration that successfully generated high levels of broadly neutralising antibodies in rhesus macaques using a germline targeting approach. The findings suggest the vaccine could potentially protect humans from HIV infection and AIDS, with plans underway to evaluate the regimen in future human clinical trials.

The vaccine works by intervening in the B cell maturation process, effectively taking ultra-rare antibody responses and turning them into common responses by the end of the vaccination process. Scientists describe B cell development as a training process, but HIV’s ability to disguise itself with sugar molecules and mutate quickly usually prevents the immune system from honing effective responses. The new approach aims to guide naive B cells to produce antibodies that recognise key HIV structures, mimicking the progression of neutralising antibodies found in rare human cases.

The research team, led by LJI Professor Shane Crotty and Scripps Research Professor William Schief, developed vaccine molecules that resembled real HIV antigens to mimic the progression of neutralising antibodies. The study involved a priming vaccine to activate naive B cells, followed by a series of shepherding booster shots to guide B cell development. This method targets naive B cells in their germline form before they begin their training process, aiming to flip the immune response so that rare protective responses become common.

Approximately 44 per cent of the primates in the study produced these abundant antibodies, which closely resembled those found in rare human cases. The antibodies were impressively abundant and found in the blood, where they could potentially encounter and block HIV. While the team did not test whether these antibodies could prevent infection in the animals, the resemblance to human broadly neutralising antibodies suggests the vaccine approach is likely to succeed in humans due to immunogenetics.

The priming immunogen used in this study was previously evaluated in humans in the HVTN 144 trial and is currently being tested in the Phase 1 trial IAVI G004. Additional recent research published in Nature Immunology reported a new strategy to accelerate related vaccine antibody responses. IAVI, Scripps Research, the HIV Vaccine Trials Network, and partners are now advancing plans to further evaluate the full immunization regimen in a future human clinical study.