Structure-based Vaccine Design in HIV: Blind Men and the Elephant?

Robert      Pejchal; Ian      A. Wilson

Abstract

Traditional vaccine approaches have failed for HIV and novel strategies are now being sought to develop immunogens designed to elicit specific activity against known broad neutralization epitopes. Structure-based vaccine design has great potential but, so far, remains a largely unproven concept. Further structural information for the envelope (Env) glycoproteins, gp120 and gp41, would be extremely beneficial, particularly for understanding trimer-specific antibodies and their epitopes and to clarify the atomic details of the structural elements responsible for masking crucial epitopes and for mediating the conformational rearrangements undertaken during the process of receptor-binding and membrane fusion.

Keywords: HIV-1 vaccine, broadly neutralizing antibodies, immunogen, HIV-1 envelope, HIV-1 trimer, gp120, gp41, Vaccine, HIV, neutralization, glycoproteins, antibodies, B cell, T cell, anti-retroviral therapy, glycosylation, monoclonal antibodies, cryoelectron tomography, Gly-Ala-Gly, CD4-induced, influenza virus, ebola virus, visna virus, human respiratory syncytial virus, T-lymphotropic virus, leukemia, SIV mac239 trimers, HJ16, VRC01, CD4 binding site, Hyperglycosylation, High-Mannose Glycan Cluster, Z13e1