Progress in HIV vaccine development

Abstract

An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials. The induction of bnAb using mimics of the natural Env trimer or B-cell lineage vaccine design is still in pre-clinical phase. An attempt at optimization of protective functional antibodies will be assessed next with the efficacy trial (HVTN702) about to start. With on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb, the prospects for a preventive HIV vaccine have never been more promising.

Keywords: HIV; RV144; broadly neutralizing antibodies; functional antibodies; vaccine.

Figure 1.

Schematic representation of potential mechanisms of protection by vaccine induced antibodies. Broadly neutralizing antibodies (BnAb) can bind to HIV virions from diverse strains, inactivating the virions. However, bnAb may not completely block mucosal portal of entry. Beyond neutralization, Abs may mediate protection through binding to cognate epitopes on HIV, immobilizing virions in mucin layers. Ab can also elicit immune responses through complement mediated lysis as well as recognition by FC receptors on effector cells (Natural Killer, NK cells and phagocytes) and mediate antibody dependent cell-mediated viral inhibition (ADCVI), including antibody dependent cytotoxicity (ADCC), Ab-dependent cellular phagocytosis (ADCP) and Ab-mediated release of cytokines or chemokines.