Importance of Fc-mediated functions of anti-HIV-1 broadly neutralizing antibodies

Anti-HIV-1 broadly neutralizing antibodies (BnAbs) exhibit an impressive capacity to protect against chimeric SIV-HIV (SHIV) challenges in macaques and potently reduce viremia in both SHIV-infected macaques and HIV-1-infected humans. There is a body of evidence suggesting Fc-mediated functions of anti-HIV-1 binding antibodies are important in protecting from infection and controlling viremia. The degree to which the efficacy of BnAbs is assisted by Fc-mediated functions is of great interest. Challenge experiments with the older generation BnAb b12 showed that mutating the Fc region to abrogate Fcγ receptor binding reduced protective efficacy in macaques. Similar data have been generated with newer BnAbs using murine models of HIV-1. In addition, the degree to which therapeutically administered BnAbs reduce viremia suggests that elimination of infected cells through Fc-mediated functions may contribute to their efficacy. Fc-mediated functions that eliminate infected cells may be particularly important for challenge systems involving cell-associated virus. Herein we review data regarding the importance of Fc-mediated functions of BnAbs in mediating protective immunity and control of viremia.