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TitleRapid elicitation of neutralizing Asn332-glycan-independent antibodies to the V3-glycan epitope of HIV-1 Env in nonhuman primates.
Journal, issue, pagesNat Immunol, Year 2026
Publish dateFeb 3, 2026
AuthorsIgnacio Relano-Rodriguez / Jianqiu Du / Zi Jie Lin / Margaret Kerwin / Marta Tarquis-Medina / Eduardo Urbano / Jiayan Cui / Meagan Watkins / Christy L Lavine / Peng Zhao / Rumi Habib / Colby Agostino / Sukanya Ghosh / Joyce Park / Caroline Boroughs / Agnes A Walsh / Mariane B Melo / Niharika Shukla / George M Shaw / Beatrice H Hahn / Darrell J Irvine / Lance Wells / David B Weiner / Michael S Seaman / Daniel W Kulp / Ronald S Veazey / Jesper Pallesen / Amelia Escolano /
PubMed AbstractSequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple ...Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. Here, we present WIN332, a new engineered Env immunogen that induces a new class of Asn332-glycan-independent antibodies to the conserved V3-glycan epitope of Env with low inhibitory activity indicative of a neutralization activity after a single bolus immunization in nonhuman primates. WIN332 binds to precursors of canonical human Asn332-glycan-dependent (type-I) V3-glycan bNAbs but also of a first-of-its-class Asn332-glycan-independent (type-II) V3-glycan bNAb. A single immunization elicits low inhibitory serum and monoclonal antibodies that are boosted and affinity matured with a heterologous immunogen. Electron microscopy polyclonal epitope mapping analysis of serum antibodies, antibody cloning and cryogenic electron microscopy analysis reveals that WIN332 elicits Asn332-glycan-independent antibodies with striking sequence and binding similarities with the most potent human type-I and type-II V3-glycan bNAbs. Thus, WIN332 is a promising vaccine candidate to streamline V3-glycan bNAb elicitation.
External linksNat Immunol / PubMed:41634485
MethodsEM (single particle)
Resolution3.79 - 3.94 Å
Structure data

EMDB-70231, PDB-9o8m:
Ab1983 in complex with HIV-1 Env variant WIN332
Method: EM (single particle) / Resolution: 3.79 Å

EMDB-70395, PDB-9oed:
Ab1999 in complex with HIV-1 Env RC1
Method: EM (single particle) / Resolution: 3.94 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN / HIV-1 Env / antibody

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