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

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 Dagotto, Makda S. Gebre, Catherine Jacob-Dolan, Zhenfeng Li, Felix Nampanya, Shivani Patel, Laurent Pessaint, Alex Ry, Kelvin Blade, Jake Yalley-Ogunro, Mehtap Cabus, Renita Brown, Anthony Cook, Elyse Teow, Hanne Andersen, Mark G. Lewis, Douglas A. Lauffenburger, Galit Alter and Dan H. Barouch ()
Additional contact information
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
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
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
Makda S. Gebre: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School
Catherine Jacob-Dolan: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, 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
Dan H. Barouch: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School

Nature, 2021, vol. 590, issue 7847, 630-634

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-020-03041-6

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