Antibodies as an Important Part of an HIV Cure Strategy
Jeffrey Laurence, M.D.
Last month, we reviewed the work of amfAR-funded scientist Dr. Nancy Haigwood of Oregon Health and Science University, who is exploring how to block mother-to-child transmission of HIV. She used a monkey model and a “passive immunotherapy” strategy based on a cocktail of two potent antibodies capable of neutralizing a broad spectrum of AIDS viruses. In the April issue of Nature Medicine, she and her colleagues wrote, “early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.” And anything that can affect HIV reservoirs is of strong interest to cure researchers.
This point is now being aggressively pursued by amfAR Krim Fellow Dr. Stylianos Bournazos and associates working in the laboratory of Dr. Jeffrey Ravetch at The Rockefeller University in New York. Writing in a May issue of the prestigious journal Science, the researchers reported utilizing a single broadly neutralizing anti-HIV antibody to target infected CD4+ T cells in mice with a humanized immune system (i.e., mice that have been injected with human stem cells). They found that the survival of infected cells could be greatly decreased by this antibody through a process involving an immune receptor known as Fc gamma.
This work is important as antibodies differ from anti-HIV drugs in that they can alter the survival times of both cell-free virus and infected cells. They can also recruit host immune cells to defend against the virus. A variety of different strains of HIV obtained directly from patients were used in this mouse model, and the antibody was equally effective against all of them. In addition, another mouse model mimicking chronic HIV infection demonstrated that such antibodies can accelerate clearance of cells after a longer-term HIV infection.
The authors concluded with this promising statement: “The finding that antibodies can clear infected cells in vivo has important implications for therapies aimed at HIV prevention and viral reservoir reduction or elimination.”
Dr. Laurence is amfAR’s senior scientific consultant.