[PDF][PDF] Elicitation of neutralizing antibodies targeting the V2 apex of the HIV envelope trimer in a wild-type animal model

JE Voss, R Andrabi, LE McCoy, N de Val, RP Fuller… - Cell reports, 2017 - cell.com
JE Voss, R Andrabi, LE McCoy, N de Val, RP Fuller, T Messmer, CY Su, D Sok, SN Khan
Cell reports, 2017cell.com
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 …
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.
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