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 Wyen; Tim 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

doi:10.1038/s41591-023-02582-3

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

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2 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 language	English
Pages (from-to)	2763-2774
Number of pages	12
Journal	Nature Medicine
Volume	29
Issue number	11
DOIs	https://doi.org/10.1038/s41591-023-02582-3
State	Published - Nov 2023

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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., ... Klein, F. (2023). Dynamics and durability of HIV-1 neutralization are determined by viral replication. Nature Medicine, 29(11), 2763-2774. https://doi.org/10.1038/s41591-023-02582-3

@article{9a81282c05ac4ff780d0a903ce53791b,

title = "Dynamics and durability of HIV-1 neutralization are determined by viral replication",

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.",

author = "Philipp Schommers and Kim, {Dae Sung} and Maike Schlotz and Christoph Kreer and Ralf Eggeling and Anna Hake and Melanie Stecher and Juyeon Park and Radford, {Caelan E.} and Dingens, {Adam S.} and Ercanoglu, {Meryem S.} and Henning Gruell and Stanley Odidika and Marten Dahlhaus and Lutz Gieselmann and Elvin Ahmadov and Lawong, {Rene Y.} and Eva Heger and Elena Knops and Christoph Wyen and Tim K{\"u}mmerle and Katja R{\"o}mer and Stefan Scholten and Timo Wolf and Christoph Stephan and Isabelle Su{\'a}rez and Nagarajan Raju and Anurag Adhikari and Stefan Esser and Hendrik Streeck and Ralf Duerr and Nanfack, {Aubin J.} and Susan Zolla-Pazner and Christof Geldmacher and Otto Geisenberger and Arne Kroidl and Wiston William and Lucas Maganga and Ntinginya, {Nyanda Elias} and Georgiev, {Ivelin S.} and Vehreschild, {J{\"o}rg J.} and Michael Hoelscher and Gerd F{\"a}tkenheuer and Lavinder, {Jason J.} and Bloom, {Jesse D.} and Seaman, {Michael S.} and Clara Lehmann and Nico Pfeifer and George Georgiou and Florian Klein",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = nov,

doi = "10.1038/s41591-023-02582-3",

language = "English",

volume = "29",

pages = "2763--2774",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "11",

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Schommers, P, Kim, DS, Schlotz, M, Kreer, C, Eggeling, R, Hake, A, Stecher, M, Park, J, Radford, CE, Dingens, AS, Ercanoglu, MS, Gruell, H, Odidika, S, Dahlhaus, M, Gieselmann, L, Ahmadov, E, Lawong, RY, 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, AJ, Zolla-Pazner, S, Geldmacher, C, Geisenberger, O, Kroidl, A, William, W, Maganga, L, Ntinginya, NE, Georgiev, IS, Vehreschild, JJ, Hoelscher, M, Fätkenheuer, G, Lavinder, JJ, Bloom, JD, Seaman, MS, Lehmann, C, Pfeifer, N, Georgiou, G & Klein, F 2023, 'Dynamics and durability of HIV-1 neutralization are determined by viral replication', Nature Medicine, vol. 29, no. 11, pp. 2763-2774. https://doi.org/10.1038/s41591-023-02582-3

TY - JOUR

T1 - Dynamics and durability of HIV-1 neutralization are determined by viral replication

AU - Schommers, Philipp

AU - Kim, Dae Sung

AU - Schlotz, Maike

AU - Kreer, Christoph

AU - Eggeling, Ralf

AU - Hake, Anna

AU - Stecher, Melanie

AU - Park, Juyeon

AU - Radford, Caelan E.

AU - Dingens, Adam S.

AU - Ercanoglu, Meryem S.

AU - Gruell, Henning

AU - Odidika, Stanley

AU - Dahlhaus, Marten

AU - Gieselmann, Lutz

AU - Ahmadov, Elvin

AU - Lawong, Rene Y.

AU - Heger, Eva

AU - Knops, Elena

AU - Wyen, Christoph

AU - Kümmerle, Tim

AU - Römer, Katja

AU - Scholten, Stefan

AU - Wolf, Timo

AU - Stephan, Christoph

AU - Suárez, Isabelle

AU - Raju, Nagarajan

AU - Adhikari, Anurag

AU - Esser, Stefan

AU - Streeck, Hendrik

AU - Duerr, Ralf

AU - Nanfack, Aubin J.

AU - Zolla-Pazner, Susan

AU - Geldmacher, Christof

AU - Geisenberger, Otto

AU - Kroidl, Arne

AU - William, Wiston

AU - Maganga, Lucas

AU - Ntinginya, Nyanda Elias

AU - Georgiev, Ivelin S.

AU - Vehreschild, Jörg J.

AU - Hoelscher, Michael

AU - Fätkenheuer, Gerd

AU - Lavinder, Jason J.

AU - Bloom, Jesse D.

AU - Seaman, Michael S.

AU - Lehmann, Clara

AU - Pfeifer, Nico

AU - Georgiou, George

AU - Klein, Florian

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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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DO - 10.1038/s41591-023-02582-3

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EP - 2774

JO - Nature Medicine

JF - Nature Medicine

IS - 11

ER -

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

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