Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody

Abstract

The acquired immunodeficiency syndrome (AIDS) is the late-stage clinical manifestation of long-term persistent infection with the human immunodeficiency virus type 1 (HIV-1). Immune responses directed against the virus and against virus-infected cells during the persistent infection fail to mediate resolution of the infection. As a result, a successful AIDS vaccine must elicit an immune state that will prevent the establishment of the persistent infection following introduction of the virus into the host. The third hypervariable (V3) domain of the HIV-1 gp120 envelope glycoprotein is a disulphide-linked closed loop of about 30 amino acids which binds and elicits anti-HIV-1 type-specific virus-neutralizing antibodies. The in vitro characteristics of anti-V3 domain antibody suggest that this antibody could by itself prevent HIV-1 infection in vivo, an idea supported by chimpanzee challenge studies in which protection against the HIV-1 persistent infection seemed to correlate with the presence of anti-V3 domain antibody. Here we directly demonstrate the protective efficacy of anti-V3 domain antibody in vivo and propose that this antibody is potentially useful as both a pre- and post-exposure prophylactic agent.