Antibody-mediated immune exclusion of HIV.

Abstract

Although approximately 90% of all HIV transmissions in humans occur through mucosal contact, the induction of mucosal anti-HIV immune responses has remained understudied. Here we summarize data demonstrating the powerful protection that is achievable at mucosal frontlines through virus-specific mucosal IgA alone or combined with IgG. Passive immunization with different monoclonal antibody subclasses but identical epitope specificity (the conserved V3-loop crown of HIV gp120) has revealed that the dimeric IgA1 (dIgA1) form with its open hinge can prevent simian-human immunodeficiency virus (SHIV) acquisition in rhesus macaques at a higher rate than dIgA2. Both dIgAs neutralized the challenge SHIV equally well. Protection was linked to better virion capture and inhibition of cell-free virus transcytosis by dIgA1. Synergistic interactions at the mucosal level between the IgG1 and dIgA2 versions of this monoclonal antibody yielded complete protection. Active vaccine strategies designed to induce mucosal IgA and systemic/mucosal IgG have given promising data. This review seeks to highlight the importance of mucosal IgAs in preventing virus acquisition. Passive immunization gave proof-of-concept for immune exclusion by mucosally administered monoclonal dIgAs. Unanswered questions remain regarding the interplay between mucosal IgA and other host immune defenses, including their induction with active immunization.