Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

Abstract

Designer Anti-HIV Developing a protective HIV vaccine remains a top global health priority. One strategy to identify potential vaccine candidates is to isolate broadly neutralizing antibodies from infected individuals and then attempt to elicit the same antibody response through vaccination (see the Perspective by Burton and Weiss ). Wu et al. (p. 856 , published online 8 July) now report the identification of three broadly neutralizing antibodies, isolated from an HIV-1–infected individual, that exhibited great breadth and potency of neutralization and were specific for the co-receptor CD4-binding site of the glycoprotein 120 (gp120), part of the viral Env spike. Zhou et al. (p. 811 , published online 8 July) analyzed the crystal structure for one of these antibodies, VRC01, in complex with an HIV-1 gp120. VRC01 focuses its binding onto a conformationally invariant domain that is the site of initial CD4 attachment, which allows the antibody to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. The epitopes recognized by these antibodies suggest potential immunogens that can inform vaccine design.