Polyfunctionality of broadly neutralizing HIV-1 antibodies

Abstract

Purpose of reviewThe discovery of broadly neutralizing HIV-1 antibodies (bNAbs) has provided a framework for vaccine design and created new hope toward an HIV-1 cure. These antibodies recognize the HIV-1 Envelope and inhibit viral fusion with unprecedented breadth and potency. Beyond their unique neutralization capacity, bNAbs also activate immune cells and interfere with viral spread through nonneutralizing activities. Here, we review the landscape of bNAbs functions and their contribution to clinical efficacy. Recent findingsParallel evaluation of bNAbs nonneutralizing activities using in vivo and in vitro models have revealed how their importance varies across antibodies and strains. Nonneutralizing bNAbs functions target both infected cells and viral particles, leading to their destruction through various mechanisms. Reservoir targeting and prevention in context of suboptimal neutralization highly depends on bNAbs polyfunctionality. We recently showed that bNAbs tether virions at the surface of infected cells, impairing release and forming immune complexes, with consequences that are still to be understood.