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

TitleElicitation of Neutralizing Antibodies Targeting the V2 Apex of the HIV Envelope Trimer in a Wild-Type Animal Model.
Publication TypeJournal Article
Year of Publication2017
AuthorsVoss JE, Andrabi R, McCoy LE, de Val N, Fuller RP, Messmer T, Su C-Y, Sok D, Khan SN, Garces F, Pritchard LK, Wyatt RT, Ward AB, Crispin M, Wilson IA, Burton DR
JournalCell Rep
Volume21
Issue1
Pagination222-235
Date Published10/03/2017
ISSN2211-1247
Abstract

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.

DOI10.1016/j.celrep.2017.09.024
Alternate JournalCell Rep
PubMed ID28978475
PubMed Central IDPMC5640805
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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