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

Publication date: 3 October 2017
Source:Cell Reports, Volume 21, Issue 1
Author(s): James E. Voss, Raiees Andrabi, Laura E. McCoy, Natalia de Val, Roberta P. Fuller, Terrence Messmer, Ching-Yao Su, Devin Sok, Salar N. Khan, Fernando Garces, Laura K. Pritchard, Richard T. Wyatt, Andrew B. Ward, Max Crispin, Ian A. Wilson, Dennis R. Burton
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.

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Teaser

Voss et al. show that select V2-apex-focusing immunogens derived from bnAb precursor neutralization-sensitive HIV isolates can reproducibly elicit autologous neutralizing responses to components of the bnAb epitope, including K169/K171 and N156, in a wild-type animal model.


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