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Here we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral activity against multiclade pseudovirus panels. 007 targets an N332\n                    <jats:sub>gp120<\/jats:sub>\n                    glycan-independent V3 epitope, a site of the HIV-1 envelope protein (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 cryogenic electron microscopy structure revealed contacts with the V3\n                    <jats:sup>324<\/jats:sup>\n                    GD\/NIR\n                    <jats:sup>327<\/jats:sup>\n                    motif and interactions with N156\n                    <jats:sub>gp120<\/jats:sub>\n                    and N301\n                    <jats:sub>gp120<\/jats:sub>\n                    glycans. In contrast to classical V3 bNAbs, 007 binding to Env does not depend on the N332\n                    <jats:sub>gp120<\/jats:sub>\n                    glycan, rendering it resistant to common escape mutations. Structures of 007 IgG-Env trimer complexes showed two Env trimers crosslinked by three bivalent IgGs. Bivalent 007 IgG was more potent than monovalent 007 IgG heterodimer, suggesting a role for avidity in potent neutralization. Finally, in HIV-1\n                    <jats:sub>ADA<\/jats:sub>\n                    -infected humanized mice, 007 caused transient decline of viremia and overcame classical V3 escape mutations, highlighting 007\u2019s potential for HIV-1 prevention, therapy, functional cure and vaccine design.\n                  <\/jats:p>","DOI":"10.1038\/s41590-025-02385-3","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:03:00Z","timestamp":1770112980000},"page":"572-585","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Identification of a potent V3 glycan site broadly neutralizing antibody targeting an N332gp120 glycan-independent 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