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-Structure paper
| タイトル | Rapid elicitation of neutralizing Asn332-glycan-independent antibodies to the V3-glycan epitope of HIV-1 Env in nonhuman primates. |
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| ジャーナル・号・ページ | Nat Immunol, Year 2026 |
| 掲載日 | 2026年2月3日 |
著者 | Ignacio 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 要旨 | 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 ...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. |
リンク | Nat Immunol / PubMed:41634485 |
| 手法 | EM (単粒子) |
| 解像度 | 3.79 - 3.94 Å |
| 構造データ | EMDB-70231, PDB-9o8m: EMDB-70395, PDB-9oed: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | VIRAL PROTEIN / HIV-1 Env / antibody |
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homo sapiens (ヒト)
human immunodeficiency virus 1 (ヒト免疫不全ウイルス)
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