Fc Receptor Binding Important for Antibody Protection Against HIV

NEW YORK (Reuters Health) Sept 05 - The findings of a new study shed light on how neutralizing antibodies protect against HIV infection and show that it is not only their ability to block viral entry that is critical. This could have important implications for the development of an effective vaccine against the pathogen, researchers conclude.

In various animal models, administration of neutralizing antibodies has been shown to protect against HIV challenge. Exactly how this occurs and whether it is solely due to the antibodies' ability to prevent viral entry has been unclear, according to the report in the September 6th issue of Nature.

Dr. Dennis R. Burton, from The Scripps Research Institute in La Jolla, California, and colleagues addressed this question by examining what happens when SHIV-challenged macaques are given neutralizing antibodies engineered to lack non-viral entry-related functions, namely their ability to bind to complement and Fc receptors on effector cells.

The authors found that removing the Fc receptor-binding function markedly impaired the antibodies' ability to protect against SHIV challenge. By contrast, removing the complement-binding function did not impair antibody efficacy.

"Our in vivo results are consistent with in vitro assays indicating that interaction of Fc-receptor-bearing effector cells with antibody-complex infected cells is important in reducing virus yield from infected cells," the researchers conclude.

"That antibodies exert their protective effect by mobilizing an allied army of immune cells may have important implications for the design of HIV vaccines," Dr. John R. Mascola, from the National Institutes of Health in Bethesda, Maryland, notes in a related editorial.

He adds that the findings also suggest that currently used assays, which only measure the neutralizing ability of antibodies, might not provide a complete picture of vaccine efficacy.

Nature 2007;449:29-30,101-105.