Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated.

The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.

Duke Scholars

Author Michael Anthony Moody Pediatrics, Infectious Diseases

Author David Charles Montefiori Surgery, Surgical Sciences

Author Feng Gao Medicine, Infectious Diseases

Author S. Munir Alam Medicine, Duke Human Vaccine Institute

Author Thomas Norton Denny Medicine, Duke Human Vaccine Institute

Author Garnett H. Kelsoe Integrative Immunobiology

Author Georgia Doris Tomaras Surgery, Surgical Sciences

Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute