In vivo protective mechanisms of neutralizing antibodies against simian immunodeficiency virus replicatio

Abstract

Identifying protective adaptive immune responses against human immunodeficiency virus type 1 (HIV-1), mainly comprising CD8+ cytotoxic T lymphocyte (CTL) and neutralizing antibody (NAb) responses, is crucial for understanding in vivo mechanisms of viral persistence and developing prophylactic/intervention strategies. In HIV-1 and pathogenic simian immunodeficiency virus (SIV) infections, CTL responses play the canonical role in primary viral replication control, whereas NAb responses are impaired. This NAb impairment in early infection conversely highlights the necessity of elucidating anti-HIV/SIV antibody defense/induction mechanisms, and one approach to analyze the impact of NAbs on HIV/SIV infection is passive immunization. We have analyzed a simian AIDS model of highly pathogenic SIVmac239-infected rhesus macaques, and characterized that a single acute-phase passive infusion of SIV-specific polyclonal NAbs drives a synergistic qualitative boosting of virus-specific T-cell responses, resulting in sustained SIV replication control. This in vivo functional augmentation of virus-specific T cells by NAbs in the SIV model provides insights into the design of protective immunity against HIV-1 infection.