Dynamics and durability of HIV-1 neutralization are determined by viral replication
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Published:2023-11
Issue:11
Volume:29
Page:2763-2774
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ISSN:1078-8956
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Container-title:Nature Medicine
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language:en
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Short-container-title:Nat Med
Author:
Schommers PhilippORCID, Kim Dae SungORCID, Schlotz Maike, Kreer ChristophORCID, Eggeling RalfORCID, Hake Anna, Stecher Melanie, Park Juyeon, Radford Caelan E., Dingens Adam S., Ercanoglu Meryem S., Gruell HenningORCID, Odidika Stanley, Dahlhaus Marten, Gieselmann Lutz, Ahmadov Elvin, Lawong Rene Y., Heger Eva, Knops ElenaORCID, Wyen Christoph, Kümmerle Tim, Römer Katja, Scholten Stefan, Wolf TimoORCID, Stephan ChristophORCID, Suárez Isabelle, Raju Nagarajan, Adhikari AnuragORCID, Esser Stefan, Streeck Hendrik, Duerr RalfORCID, Nanfack Aubin J., Zolla-Pazner SusanORCID, Geldmacher Christof, Geisenberger Otto, Kroidl ArneORCID, William Wiston, Maganga Lucas, Ntinginya Nyanda Elias, Georgiev Ivelin S., Vehreschild Jörg J., Hoelscher MichaelORCID, Fätkenheuer Gerd, Lavinder Jason J., Bloom Jesse D.ORCID, Seaman Michael S., Lehmann ClaraORCID, Pfeifer Nico, Georgiou GeorgeORCID, Klein FlorianORCID
Abstract
AbstractHuman 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.
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
Reference84 articles.
1. Zinkernagel, R.M. et al. Neutralizing antiviral antibody responses. Adv. Immunol. 79, 1–53 (2001). 2. Zohar, T. & Alter, G. Dissecting antibody-mediated protection against SARS-CoV-2. Nat. Rev. Immunol. 20, 392–394 (2020). 3. Corti, D. & Lanzavecchia, A. Broadly neutralizing antiviral antibodies. Annu. Rev. Immunol. 31, 705–742 (2013). 4. Wei, X. et al. Antibody neutralization and escape by HIV-1. Nature 422, 307–312 (2003). 5. Landais, E. & Moore, P. L. Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers. Retrovirology 15, 61 (2018).
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