We report that combination bNAb immunotherapy initiated on day 3 post-infection (PI) maintained durable CD8+ T cell–mediated suppression of SHIVAD8 viremia and preinoculation levels of CD4+ T cells in 9 of 13 treated monkeys during nearly 6 yr of observation, as assessed by successive CD8+ T cell–depletion experiments. In an extension of that study, two treatment interventions (bNAbs alone or cART plus bNAbs) beginning on week 2 PI were conducted and conferred controller status to 7 of 12 monkeys that was also dependent on control mediated by CD8+ cells. However, the median time to suppression of plasma viremia following intervention on week 2 was markedly delayed (85 wk) compared with combination bNAb immunotherapy initiated on day 3 (39 wk). In both cases, the principal correlate of virus control was the induction of CD8+ T cellular immunity.
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4 January 2021
Article|
September 23 2020
Immunotherapy during the acute SHIV infection of macaques confers long-term suppression of viremia
Yoshiaki Nishimura,
Yoshiaki Nishimura
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Olivia K. Donau,
Olivia K. Donau
Formal analysis, Investigation, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Joana Dias,
Joana Dias
Formal analysis, Investigation, Visualization, Writing - review & editing
2
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Sara Ferrando-Martinez,
Sara Ferrando-Martinez
Investigation
2
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Eric Jesteadt,
Eric Jesteadt
Formal analysis, Investigation, Visualization
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Reza Sadjadpour,
Reza Sadjadpour
Data curation, Investigation, Methodology, Project administration
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Rajeev Gautam,
Rajeev Gautam
Methodology, Validation, Writing - original draft, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Alicia Buckler-White,
Alicia Buckler-White
Formal analysis, Investigation, Methodology
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Romas Geleziunas,
Romas Geleziunas
Resources
3
Gilead Sciences, Inc., Foster City, CA
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Richard A. Koup,
Richard A. Koup
Conceptualization, Data curation, Formal analysis, Methodology, Resources, Supervision, Writing - review & editing
2
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
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Michel C. Nussenzweig,
Conceptualization, Formal analysis, Investigation, Resources, Supervision, Writing - review & editing
4
Laboratory of Molecular Immunology, Rockefeller University, New York, NY
5
Howard Hughes Medical Institute, Rockefeller University, New York, NY
Correspondence to Michel C. Nussenzweig: nussen@mail.rockefeller.edu
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Malcolm A. Martin
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Malcolm A. Martin: malm@nih.gov
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Yoshiaki Nishimura
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Olivia K. Donau
Formal analysis, Investigation, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Joana Dias
Formal analysis, Investigation, Visualization, Writing - review & editing
2
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Sara Ferrando-Martinez
Investigation
2
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Eric Jesteadt
Formal analysis, Investigation, Visualization
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Reza Sadjadpour
Data curation, Investigation, Methodology, Project administration
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Rajeev Gautam
Methodology, Validation, Writing - original draft, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Alicia Buckler-White
Formal analysis, Investigation, Methodology
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Romas Geleziunas
Resources
3
Gilead Sciences, Inc., Foster City, CA
Richard A. Koup
Conceptualization, Data curation, Formal analysis, Methodology, Resources, Supervision, Writing - review & editing
2
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Michel C. Nussenzweig
Conceptualization, Formal analysis, Investigation, Resources, Supervision, Writing - review & editing
4
Laboratory of Molecular Immunology, Rockefeller University, New York, NY
5
Howard Hughes Medical Institute, Rockefeller University, New York, NY
Malcolm A. Martin
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
Malcolm A. Martin: malm@nih.gov
Correspondence to Michel C. Nussenzweig: nussen@mail.rockefeller.edu
Received:
June 11 2020
Revision Received:
August 06 2020
Accepted:
August 18 2020
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding:
Bill and Melinda Gates Foundation
(OPP1092074)
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
(NO AWARD)
National Institute of Allergy and Infectious Diseases
(HIVRAD P01 AI100148)
National Institutes of Health
(1UM1 AI100663-01)
Robertson Foundation
(NO AWARD)
Rockefeller University
(NO AWARD)
© 2020 Nishimura et al.
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2021) 218 (1): e20201214.
Article history
Received:
June 11 2020
Revision Received:
August 06 2020
Accepted:
August 18 2020
Citation
Yoshiaki Nishimura, Olivia K. Donau, Joana Dias, Sara Ferrando-Martinez, Eric Jesteadt, Reza Sadjadpour, Rajeev Gautam, Alicia Buckler-White, Romas Geleziunas, Richard A. Koup, Michel C. Nussenzweig, Malcolm A. Martin; Immunotherapy during the acute SHIV infection of macaques confers long-term suppression of viremia. J Exp Med 4 January 2021; 218 (1): e20201214. doi: https://doi.org/10.1084/jem.20201214
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