Potent and Broadly Neutralizing Antibodies Targeting HIV Envelope Protein gp120

Abstract

Evaluation of: Pejchal R, Doores KJ, Walker LM et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334(6059), 1097–1103 (2011). A dense glycan shield of HIV Env protein gp120 protects gp120 from antibody recognition. A team of researchers at the Scripps Research Institute performed a detailed analysis of the molecular basis for the binding and neutralization activities of PGTs 127 and 128, both of which are broadly neutralizing antibodies targeting HIV gp120. Analyses indicated that PGTs 127 and 128 are able to penetrate through a gap in the glycan shield, binding to two relatively well-conserved glycans, as well as a β-strand segment of the gp120 V3 loop. Such triple binding may cross-link Env trimer spikes on the surface of HIV, resulting in enhanced neutralization potency. This paper provides great insight into the structural understanding of monoclonal antibodies that may neutralize a substantial proportion of circulating HIV strains at plausible serum concentrations.