New HIV Vaccine Could Protect Against Development of HIV Infection and AIDS

Scientists at La Jolla Institute for Immunology (LJI) have developed a new HIV vaccine that has the potential to protect humans from developing HIV infection and AIDS. It is the first vaccine to generate a high number of “broadly neutralizing,” virus-fighting antibodies in primates.

The vaccine works by intervening in a process called B cell maturation. B cells make antibodies. Yet, like many immune cells, B cells have an early “naive” stage before they are ready to make antibodies. B cells only start to mature once they get the signal that a pathogen, such as a virus, is trying to attack. B cells see pieces of that pathogen’s molecular structure and start producing antibodies that can bind to that structure and halt infection.

To develop the vaccine, the scientists studied what made the HIV-fighting B cells special and then reversed the process to see exactly how those B cells matured. By looking back at the maturation process, the researchers could track how the B cells changed when they saw specific pieces of the HIV structure. They discovered that B cells matured to make broadly neutralizing antibodies after they got an early look at parts of HIV’s outer “envelope” protein. Because these viral sites sparked an immune response, scientists would call them “antigens.” 

Since an effective HIV vaccine would likely need to include models of these antigens, they developed vaccine molecules that resembled the real HIV antigens. They then worked with Emory National Primate Research Center to test the potential HIV vaccine in a non-human primate species called rhesus macaques. The researchers first administered a “priming” vaccine meant to activate each animal’s naive B cells. The animals then received a series of “shepherding” booster shots to help their B cells develop along the right path. 

“This series of vaccinations will guide, or ‘walk’, a B cell from its naive state to its broadly neutralizing state,” says LJI Instructor Patrick Madden, PhD, who served as study co-first author with Jon Steichen, PhD, an institute investigator at Scripps Research. 

The vaccine approach is called “germline targeting” because it targets naive B cells in their “germline” or naive form, before they begin their training process.

The scientists found that approximately 44 percent of the animals went on to produce broadly neutralizing antibodies against HIV in their blood. These antibodies were impressively abundant. “We succeeded in taking ultra-rare antibody responses and turning them into common responses by the end of the vaccination process,” says LJI Professor and Chief Scientific Officer Shane Crotty, PhD, who co-led the research with Scripps Research Professor William Schief, PhD. 

The team didn’t test whether these antibodies could prevent infection, but it’s significant that these antibodies could be found in the blood, where they could encounter and potentially block HIV.