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Gieselmann, L.* ; DeLaitsch, A.T.* ; Rohde, M.* ; Radford, C.* ; Worczinski, J.* ; Ashurov, A.* ; Ahmadov, E.* ; Burger, J.A.* ; Havenar-Daughton, C.* ; Deshpande, S.* ; Giovannoni, F.* ; Corti, D.* ; Kreer, C.* ; Ercanoglu, M.S.* ; Schommers, P.* ; Georgiev, I.S.* ; West, A.P.* ; Knüfer, J.* ; Stumpf, R.* ; Kroidl, A.* ; Geldmacher, C.* ; Maganga, L.* ; William, W.* ; Ntinginya, N.E.* ; Hoelscher, M. ; Yang, Z.* ; Wei, Q.* ; Renfrow, M.B.* ; Green, T.J.* ; Novak, J.* ; van Gils, M.J.* ; Gristick, H.B.* ; Gruell, H.* ; Bloom, J.D.* ; Seaman, M.S.* ; Bjorkman, P.J.* ; Klein, F.*

Identification of a potent V3 glycan site broadly neutralizing antibody targeting an N332gp120 glycan-independent epitope.

Nat. Immunol. 27, 572-585 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Broadly neutralizing antibodies (bNAbs) against HIV-1 can suppress viremia in vivo and inform vaccine development. Here we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral activity against multiclade pseudovirus panels. 007 targets an N332gp120 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 324GD/NIR327 motif and interactions with N156gp120 and N301gp120 glycans. In contrast to classical V3 bNAbs, 007 binding to Env does not depend on the N332gp120 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-1ADA-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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cryo-em; Monoclonal-antibodies; Crystal-structure; Hiv-1; Recognition; Env; Generation; Refinement; Increases; Viremia
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Journal Nature Immunology
Quellenangaben Volume: 27, Issue: 3, Pages: 572-585 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Research Unit Global Health (UGH)
Grants EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)
Deutsche Forschungsgemeinschaft (German Research Foundation)
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation)