Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.

Journal: Science Translational Medicine
Published:
Abstract

A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man9-V3). V3-glycan bnAbs bound to Man9-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man9-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man9-V3 induced V3-glycan-targeted antibodies. Thus, the Man9-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.

Authors
S Alam, Baptiste Aussedat, Yusuf Vohra, R Meyerhoff, Evan Cale, William Walkowicz, Nathan Radakovich, Kara Anasti, Lawrence Armand, Robert Parks, Laura Sutherland, Richard Scearce, M Joyce, Marie Pancera, Aliaksandr Druz, Ivelin Georgiev, Tarra Von Holle, Amanda Eaton, Christopher Fox, Steven Reed, Mark Louder, Robert Bailer, Lynn Morris, Salim Abdool Karim, Myron Cohen, Hua-xin Liao, David Montefiori, Peter Park, Alberto Fernández Tejada, Kevin Wiehe, Sampa Santra, Thomas Kepler, Kevin Saunders, Joseph Sodroski, Peter Kwong, John Mascola, Mattia Bonsignori, M Moody, Samuel Danishefsky, Barton Haynes
Relevant Conditions

HIV/AIDS