Antibody Epitope Exposure and Neutralization of HIV-1

Formulating an effective HIV vaccine remains a formidable challenge despite nearly 3 decades of intense research since the virus was first isolated. One of the obstacles that need to be surmounted is the design of a preparation that elicits a potent and broadly neutralizing antibody (nAb) response, i.e. antibodies with the capacity to block infectivity of the genetically diverse pool of HIV strains that circulate globally. The primary target for nAbs on HIV-1 is the envelope glycoprotein spike (Env). Early work on elucidating the exposure of antibody epitopes on Env suggested highly restricted accessibility of antibodies to epitopes that are conserved among otherwise diverse virus isolates. Crystal structures of Env-derived antigens, most in complex with antibodies, along with structure-function studies and molecular modeling, have provided significant further insight into features of Env that limit broad antibody recognition. Despite these challenges, recent progress on various fronts has led to a growing sense that Env is not as impenetrable to nAbs as might have been believed in the past. Increased understanding of antibody epitope exposure on Env should provide new impulses for efforts to elicit nAbs that can protect against HIV-1 infection.