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Schommers, P.* ; Kim, D.S.* ; Schlotz, M.* ; Kreer, C.* ; Eggeling, R.* ; Hake, A.* ; Stecher, M.* ; Park, J.* ; Radford, C.E.* ; Dingens, A.S.* ; Ercanoglu, M.S.* ; Gruell, H.* ; Odidika, S.* ; Dahlhaus, M.* ; Gieselmann, L.* ; Ahmadov, E.* ; Lawong, R.Y.* ; Heger, E.* ; Knops, E.* ; Wyen, C.* ; Kümmerle, T.* ; Römer, K.* ; Scholten, S.* ; Wolf, T.* ; Stephan, C.* ; Suárez, I.* ; Raju, N.* ; Adhikari, A.* ; Esser, S.* ; Streeck, H.* ; Duerr, R.* ; Nanfack, A.J.* ; Zolla-Pazner, S.* ; Geldmacher, C.* ; Geisenberger, O.* ; Kroidl, A.* ; William, W.* ; Maganga, L.* ; Ntinginya, N.E.* ; Georgiev, I.S.* ; Vehreschild, J.J.* ; Hoelscher, M. ; Fätkenheuer, G.* ; Lavinder, J.J.* ; Bloom, J.D.* ; Seaman, M.S.* ; Lehmann, C.* ; Pfeifer, N.* ; Georgiou, G.* ; Klein, F.*

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Nat. Med. 29, 2763-2774 (2023)

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Open Access Green as soon as Postprint is submitted to ZB.

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Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4⁺ T cell counts <200 µl^-1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Immunodeficiency-virus Type-1; Monoclonal-antibodies; Serum; Responses; Escape; Broad; Panel; Association; Specificity; Repertoire

ISSN (print) / ISBN 1078-8956

e-ISSN 1546-170X

Journal Nature medicine

Quellenangaben Volume: 29, Issue: 11, Pages: 2763-2774

Publisher Nature Publishing Group

Publishing Place New York, NY

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Unit Global Health (UGH)

Grants Universität zu Köln