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-Structure paper
| タイトル | Identification of a broad and potent V3 glycan site bNAb targeting an N332 glycan-independent epitope. |
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| ジャーナル・号・ページ | bioRxiv, Year 2025 |
| 掲載日 | 2025年9月10日 |
著者 | Lutz Gieselmann / Andrew T DeLaitsch / Malena Rohde / Caelan Radford / Johanna Worczinski / Anna Momot / Elvin Ahmadov / Judith A Burger / Colin Havenar-Daughton / Sharvari Deshpande / Federico Giovannoni / Davide Corti / Christoph Kreer / Meryem Seda Ercanoglu / Philipp Schommers / Ivelin S Georgiev / Anthony P West / Jacqueline Knüfer / Ricarda Stumpf / Arne Kroidl / Christof Geldmacher / Lucas Maganga / Wiston William / Nyanda E Ntinginya / Michael Hoelscher / Zhengrong Yang / Qing Wei / Matthew Renfrow / Todd J Green / Jan Novak / Marit J van Gils / Harry B Gristick / Henning Gruell / Jesse D Bloom / Michael S Seaman / Pamela J Bjorkman / Florian Klein / ![]() |
| PubMed 要旨 | Broadly neutralizing antibodies (bNAbs) against HIV-1 can suppress viremia and inform vaccine development. Here, we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral ...Broadly neutralizing antibodies (bNAbs) against HIV-1 can suppress viremia and inform vaccine development. Here, we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral activity against multiclade pseudovirus panels (GeoMean IC = 0.012 μg/mL, breadth = 69%, 217 virus strains) by targeting a N332 glycan-independent V3 epitope, a site of Env vulnerability to which only weakly neutralizing antibodies had previously been identified. Functional analyses demonstrated distinct binding and neutralization profiles compared to classical V3 glycan site bNAbs. A 007 Fab-Env cryo-EM structure revealed contacts with the V3 GD/NIR motif and interactions with N156 and N301 glycans. In contrast to classical V3 bNAbs, 007 binding to Env does not depend on the N332 glycan, rendering it resistant to common escape mutations. Structures of 007 IgG-Env trimer complexes showed two Env trimers crosslinked by three bivalent IgGs, and bivalent 007 IgG was up to ~300-fold more potent than monovalent 007 IgG heterodimer, suggesting a role for avidity in potent neutralization. Finally, in HIV-1-infected humanized mice, 007 caused transient decline of viremia and overcame classical V3 escape mutations, highlighting 007's potential for HIV-1 prevention, therapy, functional cure, and vaccine design. |
リンク | bioRxiv / PubMed:40964353 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.9 - 4.2 Å |
| 構造データ | EMDB-70018, PDB-9o2q: EMDB-70019, PDB-9o2r: EMDB-70020, PDB-9o2s: EMDB-70021, PDB-9o2t: EMDB-70022, PDB-9o2u: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | VIRAL PROTEIN / Envelope / SOSIP / trimer / VIRAL PROTEIN/IMMUNE SYSTEM / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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human immunodeficiency virus 1 (ヒト免疫不全ウイルス)
homo sapiens (ヒト)
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