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

Philipp Schommers, Dae Sung Kim, Maike Schlotz, Christoph Kreer, Ralf Eggeling, Anna Hake, Melanie Stecher, Juyeon Park, Caelan E. Radford, Adam S. Dingens, Meryem S. Ercanoglu, Henning Gruell, Stanley Odidika, Marten Dahlhaus, Lutz Gieselmann, Elvin Ahmadov, Rene Y. Lawong, Eva Heger, Elena Knops, Christoph WyenTim Kümmerle, Katja Römer, Stefan Scholten, Timo Wolf, Christoph Stephan, Isabelle Suárez, Nagarajan Raju, Anurag Adhikari, Stefan Esser, Hendrik Streeck, Ralf Duerr, Aubin J. Nanfack, Susan Zolla-Pazner, Christof Geldmacher, Otto Geisenberger, Arne Kroidl, Wiston William, Lucas Maganga, Nyanda Elias Ntinginya, Ivelin S. Georgiev, Jörg J. Vehreschild, Michael Hoelscher, Gerd Fätkenheuer, Jason J. Lavinder, Jesse D. Bloom, Michael S. Seaman, Clara Lehmann, Nico Pfeifer, George Georgiou, Florian Klein

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2763-2774
Number of pages12
JournalNature Medicine
Volume29
Issue number11
DOIs
StatePublished - Nov 2023

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