3 years ago

Elicitation of Neutralizing Antibodies Targeting the V2 Apex of the HIV Envelope Trimer in a Wild-Type Animal Model

Elicitation of Neutralizing Antibodies Targeting the V2 Apex of the HIV Envelope Trimer in a Wild-Type Animal Model
Laura K. Pritchard, Roberta P. Fuller, Andrew B. Ward, Richard T. Wyatt, Terrence Messmer, James E. Voss, Laura E. McCoy, Fernando Garces, Devin Sok, Dennis R. Burton, Ching-Yao Su, Raiees Andrabi, Ian A. Wilson, Max Crispin, Natalia de Val, Salar N. Khan

Summary

Recent efforts toward HIV vaccine development include the design of immunogens that can engage B cell receptors with the potential to affinity mature into broadly neutralizing antibodies (bnAbs). V2-apex bnAbs, which bind a protein-glycan region on HIV envelope glycoprotein (Env) trimer, are among the most broad and potent described. We show here that a rare "glycan hole" at the V2 apex is enriched in HIV isolates neutralized by inferred precursors of prototype V2-apex bnAbs. To investigate whether this feature could focus neutralizing responses onto the apex bnAb region, we immunized wild-type rabbits with soluble trimers adapted from these Envs. Potent autologous tier 2 neutralizing responses targeting basic residues in strand C of the V2 region, which forms the core epitope for V2-apex bnAbs, were observed. Neutralizing monoclonal antibodies (mAbs) derived from these animals display features promising for subsequent broadening of the response.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31299-8

DOI: 10.1016/j.celrep.2017.09.024

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