New approaches to HIV vaccine development

Abstract

Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design.

Figure 1. Sites of vulnerability on the HIV glycoprotein spike

The structure of a HIV pre-fusion trimer is displayed with gp120 and gp41 protomers colored in dark and light gray, respectively. The five common specificities of isolated bnAbs are: V1/V2 loop (green), the base of the V3 loop (blue), the CD4-binding site (magenta), gp120-gp41 bridging region (red), and the membrane proximal external region (orange). The MPER near the base of the Env trimer near the viral membrane has only limited structural information and is highlighted for reference (orange lines). Below each bnAb site are listed prototype antibodies that can bind at each site. Adapted with permission from Pancera et al. Nature, 2014; PDB: 4TVP.