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

• Published in: Nature (London) Vol. 590; no. 7847; pp. 630 - 634
• Main Authors: McMahan, Katherine, Yu, Jingyou, Mercado, Noe B., Loos, Carolin, Tostanoski, Lisa H., Chandrashekar, Abishek, Liu, Jinyan, Peter, Lauren, Atyeo, Caroline, Zhu, Alex, Bondzie, Esther A., Dagotto, Gabriel, Gebre, Makda S., Jacob-Dolan, Catherine, Li, Zhenfeng, Nampanya, Felix, Patel, Shivani, Pessaint, Laurent, Van Ry, Alex, Blade, Kelvin, Yalley-Ogunro, Jake, Cabus, Mehtap, Brown, Renita, Cook, Anthony, Teow, Elyse, Andersen, Hanne, Lewis, Mark G., Lauffenburger, Douglas A., Alter, Galit, Barouch, Dan H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.02.2021; Nature Publishing Group
• Subjects: 13/1; 631/250/2152/1566; 631/250/2152/2153/1291; 631/326/596/4130; 64; Adoptive Transfer; Analysis; Animals; Antibodies; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; Cell-mediated immunity; Chemical compounds; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 - therapy; COVID-19 - virology; COVID-19 Serotherapy; Depletion; Disease Models, Animal; Experiments; Female; Humanities and Social Sciences; Humoral immunity; Immune response; Immunity; Immunization, Passive; Immunoglobulin G; Immunoglobulin G - administration & dosage; Immunoglobulin G - analysis; Immunoglobulin G - immunology; Infections; Lavage; Lymphocytes; Lymphocytes T; Macaca mulatta - immunology; Macaca mulatta - virology; Male; Methods; multidisciplinary; Pharmacology; Principal components analysis; Regression Analysis; Respiration; Respiratory diseases; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Vaccination; Vaccines; Viral diseases; Viral Load - immunology; United States
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-020-03041-6

Recent studies have reported the protective efficacy of both natural 1 and vaccine-induced 2 – 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. Adoptive transfer of purified IgG from convalescent macaques protects naive macaques against SARS-CoV-2 infection, and cellular immune responses contribute to protection against rechallenge with SARS-CoV-2.