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

被引：1

作者：

Schommers, Philipp ^{[1
,2
,3
,4
,5
]}

Kim, Dae Sung ^{[6
]}

Schlotz, Maike ^{[1
,2
]}

Kreer, Christoph ^{[1
,2
]}

Eggeling, Ralf ^{[7
,8
]}

Hake, Anna ^{[9
,10
]}

Stecher, Melanie ^{[3
,5
]}

Park, Juyeon ^{[11
]}

Radford, Caelan E. ^{[12
,13
]}

Dingens, Adam S. ^{[13
]}

Ercanoglu, Meryem S. ^{[1
,2
]}

Gruell, Henning ^{[1
,2
]}

Odidika, Stanley ^{[2
,3
,4
]}

Dahlhaus, Marten ^{[2
,3
,4
]}

Gieselmann, Lutz ^{[1
,2
,5
]}

Ahmadov, Elvin ^{[1
,2
]}

Lawong, Rene Y. ^{[1
,2
]}

Heger, Eva ^{[1
,2
]}

Knops, Elena ^{[1
,2
]}

Wyen, Christoph ^{[2
,3
,14
]}

Kuemmerle, Tim ^{[14
]}

Roemer, Katja ^{[15
]}

Scholten, Stefan ^{[16
]}

Wolf, Timo ^{[17
]}

Stephan, Christoph ^{[17
]}

Suarez, Isabelle ^{[3
,5
]}

Raju, Nagarajan ^{[18
,19
]}

Adhikari, Anurag ^{[20
]}

Esser, Stefan ^{[21
]}

Streeck, Hendrik ^{[5
,22
]}

Duerr, Ralf ^{[23
,24
,25
]}

Nanfack, Aubin J. ^{[26
,27
]}

Zolla-Pazner, Susan ^{[28
,29
]}

Geldmacher, Christof ^{[30
,31
,32
]}

Geisenberger, Otto ^{[30
,31
]}

Kroidl, Arne ^{[30
,31
]}

William, Wiston ^{[33
]}

Maganga, Lucas ^{[33
]}

Ntinginya, Nyanda Elias ^{[33
]}

Georgiev, Ivelin S. ^{[18
,19
,34
,35
,36
]}

Vehreschild, Joerg J. ^{[3
,5
]}

Hoelscher, Michael ^{[30
,31
,32
,37
]}

Faetkenheuer, Gerd ^{[2
,3
,5
]}

Lavinder, Jason J. ^{[11
,38
]}

Bloom, Jesse D. ^{[13
,39
]}

Seaman, Michael S. ^{[40
]}

Lehmann, Clara ^{[3
,4
,5
]}

Pfeifer, Nico ^{[7
,8
]}

Georgiou, George ^{[6
,11
,38
]}

Klein, Florian ^{[1
,2
,4
,5
]}

机构：

[1] Univ Cologne, Inst Virol, Fac Med, Cologne, Germany

[2] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[3] Univ Cologne, Fac Med, Dept Internal Med 2, Cologne, Germany

[4] Ctr Mol Med Cologne CMMC, Cologne, Germany

[5] German Ctr Infect Res DZ, Cologne, Germany

[6] Univ Texas Austin, Dept Biomed Engn, Austin, TX USA

[7] Univ Tubingen, Dept Comp Sci, Methods Med Informat, Tubingen, Germany

[8] Univ Tubingen, Inst Bioinformat & Med Informat, Tubingen, Germany

[9] Max Planck Inst Informat, Max Planck Res Grp Computat Genom & Epidemiol, Saarbrucken, Germany

[10] Saarland Informat Campus, Saarbrucken, Germany

[11] Univ Texas Austin, Dept Mol Biosci, Austin, TX USA

[12] Univ Washington, Fred Hutch Canc Ctr, Mol & Cellular Biol Grad Program, Basic Sci Div, Seattle, WA USA

[13] Fred Hutchinson Canc Ctr, Computat Biol Program, Basic Sci Div, Seattle, WA USA

[14] Praxis Ebertplatz, Cologne, Germany

[15] Gemeinschaftspraxis Gotenring, Cologne, Germany

[16] Praxis Hohenstaufenring, Cologne, Germany

[17] Goethe Univ, Univ Hosp Frankfurt, Dept Infect Dis, Frankfurt, Germany

[18] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37212 USA

[19] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN USA

[20] Kathmandu Res Inst Biol Sci, Dept Infect & Immunol, Lalitpur, Nepal

[21] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, Essen, Germany

[22] Univ Bonn, Inst Virol, Med Fac, Bonn, Germany

[23] NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA

[24] NYU, Dept Med, Grossman Sch Med, New York, NY 10016 USA

[25] NYU, Grossman Sch Med, Langone Vaccine Ctr, New York, NY 10003 USA

[26] Med Diagnost Ctr, Yaounde, Cameroon

[27] Chantal Biya Int Reference Ctr Res HIV AIDS Preven, AIDS Prevent & Management CIRCB, Yaounde, Cameroon

[28] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY USA

[29] NYU, Sch Med, Dept Med, New York, NY USA

[30] Univ Hosp Munich LMU, Div Infect Dis & Trop Med, Munich, Germany

[31] German Ctr Infect Res DZIF, Partner Site Munich, Munich, Germany

[32] Fraunhofer Inst Translat Med & Pharmacol ITMP, Immunol Infect & Pandem Res, Munich, Germany

[33] Natl Inst Med Res Mbeya Med Res Ctr, Mbeya, Tanzania

[34] Vanderbilt Univ Sch Med, Vanderbilt Inst Infect, Immunol & Inflammat, Nashville, TN USA

[35] Vanderbilt Univ, Dept Comp Sci, Nashville, TN USA

[36] Vanderbilt Univ, Ctr Struct Biol, Nashville, TN USA

[37] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth HMGU, Neuherberg, Germany

[38] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA

[39] Howard Hughes Med Inst, Seattle, WA 98109 USA

[40] Ctr Virol & Vaccine Res, Beth Israel Deaconess Med Ctr, Harvard Med Sch, Boston, MA USA

来源：

NATURE MEDICINE | 2023年 / 29卷 / 11期

基金：

美国国家卫生研究院; 欧洲研究理事会; 比尔及梅琳达.盖茨基金会;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; MONOCLONAL-ANTIBODIES; SERUM; RESPONSES; ESCAPE; BROAD; PANEL; ASSOCIATION; SPECIFICITY; REPERTOIRE;

D O I：

10.1038/s41591-023-02616-w

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 mu l(-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.

引用

页码：2684 / 2685

页数：2

共 50 条

[1] 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
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