Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide
- Alam, S. Munir
- Aussedat, Baptiste
- Vohra, Yusuf
- Meyerhoff, R. Ryan
- Cale, Evan M.
- Walkowicz, William E.
- Radakovich, Nathan A.
- Anasti, Kara
- Armand, Lawrence
- Parks, Robert
- Sutherland, Laura
- Scearce, Richard
- Joyce, M. Gordon
- Pancera, Marie
- Druz, Aliaksandr
- Georgiev, Ivelin S.
- Von Holle, Tarra
- Eaton, Amanda
- Fox, Christopher
- Reed, Steven G.
- Louder, Mark
- Bailer, Robert T.
- Morris, Lynn
- Abdool-Karim, Salim S.
- Cohen, Myron
- Liao, Hua-Xin
- Montefiori, David C.
- Park, Peter K.
- Fernández-Tejada, Alberto
- Wiehe, Kevin
- Santra, Sampa
- Kepler, Thomas B.
- Saunders, Kevin O.
- Sodroski, Joseph
- Kwong, Peter D.
- Mascola, John R.
- Bonsignori, Mattia
- Moody, M. Anthony
- Danishefsky, Samuel
- Haynes, Barton F.
DOIAbstract
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 glycopeptid...
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