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Gieselmann, L.* ; DeLaitsch, A.T.* ; Rohde, M.* ; Gruell, H.* ; Kreer, C.* ; Ercanoglu, M.S.* ; Gristick, H.B.* ; Schommers, P.* ; Ahmadov, E.* ; Radford, C.E.* ; Mazzolini, A.* ; Zhang, L.* ; West, A.P.* ; Worczinski, J.* ; Momot, A.* ; Reichwein, M.L.* ; Knüfer, J.* ; Stumpf, R.* ; Mkhize, N.N.* ; Kaldine, H.* ; Bhebhe, S.* ; Deshpande, S.* ; Giovannoni, F.* ; Stefanutti, E.* ; Benigni, F.* ; Havenar-Daughton, C.* ; Corti, D.* ; Kroidl, A.* ; Adhikari, A.* ; Nanfack, A.J.* ; Ambada, G.E.* ; Duerr, R.* ; Maganga, L.* ; William, W.* ; Ntinginya, N.E.* ; Wolf, T.* ; Geldmacher, C.* ; Hoelscher, M. ; Lehmann, C.* ; Moore, P.L.* ; Mora, T.* ; Walczak, A.M.* ; Gilbert, P.B.* ; Doria-Rose, N.A.* ; Huang, Y.* ; Bloom, J.D.* ; Seaman, M.S.* ; Bjorkman, P.J.* ; Klein, F.*

Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bnAb for HIV-1 prevention and therapy.

Nat. Immunol., DOI: 10.1038/s41590-025-02286-5 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Administration of HIV-1 neutralizing antibodies can suppress viremia and prevent infection in vivo. However, clinical use is challenged by envelope diversity and rapid viral escape. Here, we performed single B cell profiling of 32 top HIV-1 elite neutralizers to identify broadly neutralizing antibodies with highest antiviral activity. From 831 expressed monoclonal antibodies, we identified 04_A06, a VH1-2-encoded broadly neutralizing antibody to the CD4 binding site with remarkable breadth and potency against multiclade pseudovirus panels (geometric mean half-maximal inhibitory concentration = 0.059 µg ml-1, breadth = 98.5%, 332 strains). Moreover, 04_A06 was not susceptible to classic CD4 binding site escape variants and maintained full viral suppression in HIV-1-infected humanized mice. Structural analyses revealed an unusually long 11-amino-acid heavy chain insertion that facilitates interprotomer contacts with highly conserved residues on the adjacent gp120 protomer. Finally, 04_A06 demonstrated high activity against contemporaneously circulating viruses from the Antibody-Mediated Prevention trials (geometric mean half-maximal inhibitory concentration = 0.082 µg ml-1, breadth = 98.4%, 191 virus strains), and in silico modeling for 04_A06LS predicted prevention efficacy of >93%. Thus, 04_A06 will provide unique opportunities for effective treatment and prevention of HIV-1 infection.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Monoclonal-antibodies; Structural Basis; Broad; Panel; Glycoproteins; Recognition; Sequence; Escape; Model; Site
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Global Health (UGH)
Förderungen Emmy Noether Programme of the German Research Foundation
Bill and Melinda Gates Foundation
European Research Council (ERC)
German Research Foundation
NIH AIDS Reagent Program - German Center of Infection Research (DZIF)
NSF Graduate Research Fellowship
Caltech Cryo-EM Center
Grant conditions of the Foundation
Agence Nationale de la Recherche
European Research Council
Bill and Melinda Gates Foundation's Collaboration for AIDS Vaccine Discovery
National Research Foundation
South African Research Chairs Initiative of the Department of Science and Innovation
National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Deutsche Forschungsgemeinschaft (German Research Foundation)