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Correlates of protection against SARS-CoV-2 in rhesus macaques

Author

Listed:
  • Katherine McMahan

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Jingyou Yu

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Noe B. Mercado

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Carolin Loos

    (Ragon Institute of MGH, MIT and Harvard
    Massachusetts Institute of Technology)

  • Lisa H. Tostanoski

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Abishek Chandrashekar

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Jinyan Liu

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Lauren Peter

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Caroline Atyeo

    (Ragon Institute of MGH, MIT and Harvard
    Harvard Medical School)

  • Alex Zhu

    (Ragon Institute of MGH, MIT and Harvard)

  • Esther A. Bondzie

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Gabriel Dagotto

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
    Harvard Medical School)

  • Makda S. Gebre

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
    Harvard Medical School)

  • Catherine Jacob-Dolan

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
    Harvard Medical School)

  • Zhenfeng Li

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Felix Nampanya

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Shivani Patel

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Laurent Pessaint

    (Bioqual)

  • Alex Ry

    (Bioqual)

  • Kelvin Blade

    (Bioqual)

  • Jake Yalley-Ogunro

    (Bioqual)

  • Mehtap Cabus

    (Bioqual)

  • Renita Brown

    (Bioqual)

  • Anthony Cook

    (Bioqual)

  • Elyse Teow

    (Bioqual)

  • Hanne Andersen

    (Bioqual)

  • Mark G. Lewis

    (Bioqual)

  • Douglas A. Lauffenburger

    (Massachusetts Institute of Technology)

  • Galit Alter

    (Ragon Institute of MGH, MIT and Harvard
    Massachusetts Consortium on Pathogen Readiness)

  • Dan H. Barouch

    (Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
    Ragon Institute of MGH, MIT and Harvard
    Harvard Medical School
    Massachusetts Consortium on Pathogen Readiness)

Abstract

Recent studies have reported the protective efficacy of both natural1 and vaccine-induced2–7 immunity against challenge with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in rhesus macaques. However, the importance of humoral and cellular immunity for protection against infection with SARS-CoV-2 remains to be determined. Here we show that the adoptive transfer of purified IgG from convalescent rhesus macaques (Macaca mulatta) protects naive recipient macaques against challenge with SARS-CoV-2 in a dose-dependent fashion. Depletion of CD8+ T cells in convalescent macaques partially abrogated the protective efficacy of natural immunity against rechallenge with SARS-CoV-2, which suggests a role for cellular immunity in the context of waning or subprotective antibody titres. These data demonstrate that relatively low antibody titres are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may contribute to protection if antibody responses are suboptimal. We also show that higher antibody titres are required for treatment of SARS-CoV-2 infection in macaques. These findings have implications for the development of SARS-CoV-2 vaccines and immune-based therapeutic agents.

Suggested Citation

  • Katherine McMahan & Jingyou Yu & Noe B. Mercado & Carolin Loos & Lisa H. Tostanoski & Abishek Chandrashekar & Jinyan Liu & Lauren Peter & Caroline Atyeo & Alex Zhu & Esther A. Bondzie & Gabriel Dagott, 2021. "Correlates of protection against SARS-CoV-2 in rhesus macaques," Nature, Nature, vol. 590(7847), pages 630-634, February.
    • Handle: RePEc:nat:nature:v:590:y:2021:i:7847:d:10.1038_s41586-020-03041-6
    DOI: 10.1038/s41586-020-03041-6
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    Cited by:

    1. Vincent Pavot & Catherine Berry & Michael Kishko & Natalie G. Anosova & Lu Li & Tim Tibbitts & Dean Huang & Alice Raillard & Sylviane Gautheron & Cindy Gutzeit & Marguerite Koutsoukos & Roman M. Chicz, 2023. "Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-8, December.
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    9. Laurent Renia & Yun Shan Goh & Angeline Rouers & Nina Bert & Wan Ni Chia & Jean-Marc Chavatte & Siew‐Wai Fong & Zi Wei Chang & Nicole Ziyi Zhuo & Matthew Zirui Tay & Yi-Hao Chan & Chee Wah Tan & Nicho, 2022. "Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Min-Seok Rha & Gyeongyeob Kim & Sol Lee & Jihye Kim & Yeonsu Jeong & Chan Min Jung & Hae Eun Noh & Ji Yun Noh & Yong Min Kim & Hyung-Ju Cho & Chang-Hoon Kim & Eui-Cheol Shin, 2024. "SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions with enhanced IFN-γ production," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    11. Youyi Fong & Yunda Huang & David Benkeser & Lindsay N. Carpp & Germán Áñez & Wayne Woo & Alice McGarry & Lisa M. Dunkle & Iksung Cho & Christopher R. Houchens & Karen Martins & Lakshmi Jayashankar & F, 2023. "Immune correlates analysis of the PREVENT-19 COVID-19 vaccine efficacy clinical trial," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Dapeng Li & David R. Martinez & Alexandra Schäfer & Haiyan Chen & Maggie Barr & Laura L. Sutherland & Esther Lee & Robert Parks & Dieter Mielke & Whitney Edwards & Amanda Newman & Kevin W. Bock & Mahn, 2022. "Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Guiomar Casado-Fernández & Magdalena Corona & Montserrat Torres & Adolfo J. Saez & Fernando Ramos-Martín & Mario Manzanares & Lorena Vigón & Elena Mateos & Francisco Pozo & Inmaculada Casas & Valentín, 2023. "Sustained Cytotoxic Response of Peripheral Blood Mononuclear Cells from Unvaccinated Individuals Admitted to the ICU Due to Critical COVID-19 Is Essential to Avoid a Fatal Outcome," IJERPH, MDPI, vol. 20(3), pages 1-19, January.
    14. Payton A.-B. Weidenbacher & Mrinmoy Sanyal & Natalia Friedland & Shaogeng Tang & Prabhu S. Arunachalam & Mengyun Hu & Ozan S. Kumru & Mary Kate Morris & Jane Fontenot & Lisa Shirreff & Jonathan Do & Y, 2023. "A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
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    17. Li Wang & Markus H. Kainulainen & Nannan Jiang & Han Di & Gaston Bonenfant & Lisa Mills & Michael Currier & Punya Shrivastava-Ranjan & Brenda M. Calderon & Mili Sheth & Brian R. Mann & Jaber Hossain &, 2022. "Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
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