New concepts in HIV-1 vaccine development

Abstract

With 2 million people newly infected with HIV-1 in 2014, an effective HIV-1 vaccine remains a major public health priority. HIV-1 vaccine efficacy trials in humans, complemented by active and passive immunization studies in non-human primates, have identified several key vaccine-induced immunological responses that may correlate with protection against HIV-1 infection. Potential correlates of protection in these studies include V2-specific, polyfunctional, and broadly neutralizing antibody responses, as well as effector memory T cell responses. Here we review how these correlates of protection are guiding current approaches to HIV-1 vaccine development. These approaches include improvements on the ALVAC-HIV/AIDSVAX B/E vaccine regimen used in the RV144 clinical trial in Thailand, adenovirus serotype 26 vectors with gp140 boosting, intravenous infusions of bNAbs, and replicating viral vectors.

Figure 1. Potential correlates of protection for ongoing HIV vaccine studies

(1) V1V2-specific and/or polyfunctional non-neutralizing antibodies (NnAb, left panel). The cartoon represents the mechanism by which non-neutralizing antibodies may bind to infected CD4+ T cells, triggering complement activation, antibody-dependent cellular phagocytosis (ADCP), and/or antibody-dependent cellular cytotoxicity (ADCC). (2) Broadly neutralizing antibodies (nAb, middle panel). The cartoon represents neutralization of the infecting virus via binding to the Envelope glycoprotein. (C) Effector memory T-cells at mucosal sites. The cartoon depicts continuous antigen stimulation via an effector memory T-cell pool.