A minority of people living with HIV naturally develop broadly neutralizing antibodies (bNAbs), which can stop a wide range of HIV strains from infecting human cells in the laboratory. Determining whether bNAbs can protect uninfected people from HIV infection is an important area of current study. To explore this novel method of prevention, scientists are pursuing a strategy called passive antibody transfer. While an HIV vaccine aims to stimulate the immune system to produce antibodies against HIV, passive antibody transfer involves giving anti-HIV bNAbs directly to an uninfected person by injections or intravenous infusions prior to HIV exposure to neutralize the virus and prevent HIV infection. Scientists have shown that the technique can protect monkeys from infection with simian human immunodeficiency virus, which contains components of HIV and the related monkey virus.
The bNAb VRC01 has been tested in passive antibody transfer studies in both animals and humans. NIAID scientists originally discovered VRC01 in the blood of a slow progressor, a person able to control HIV infection without medicine for many years before needing antiretroviral therapy. Initial passive antibody transfer studies in humans showed that administering VRC01 is safe, and NIAID is planning further studies to determine whether this bNAb is effective at preventing HIV infection in people. In April 2016, NIAID launched the first of two planned multinational clinical trials known as the AMP Studies. These trials aim to determine whether giving people an intravenous infusion of VRC01 every 8 weeks is safe, tolerable, and effective at preventing HIV infection.
Researchers also are performing experiments to see if they can boost antibody potency and lengthen the time that bNAbs last in the body, with the goal of reducing the dosage that patients would need if passive antibody transfer proves effective at HIV prevention. To this end, NIAID scientists and colleagues modified VRC01. When infused into monkeys, the modified version lasted longer in the blood and persisted longer in rectal mucosal tissue than the unaltered bNAbs. Additional research is focusing on devising ways to concentrate anti-HIV bNAbs at the mucosal surfaces of the rectum and vagina, a critical strategy for blocking sexual transmission of HIV.
In late 2015, NIAID announced a new initiative to evaluate and work to improve known and novel HIV bNAbs, and identify combinations of bNAbs capable of blocking the widest range of HIV strains. Partnering with the global pharmaceutical company GlaxoSmithKline, NIAID researchers will evaluate bNAbs discovered at NIAID to determine which ones are the most promising for development of long-acting prevention and treatment tools.