Correlates of Protection Against SARS-CoV-2 in Rhesus Macaques

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.

Recent studies have reported protective efficacy of both natural immunity1 and vaccine-induced immunity(2–7) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge in rhesus macaques. However, the importance of humoral and cellular immunity for protection against SARS-CoV-2 infection remains to be determined. Here we show that adoptive transfer of purified IgG from convalescent macaques protects naïve recipient rhesus macaques against SARS-CoV-2 challenge in a dose dependent fashion. Depletion of CD8+ T cells in convalescent animals partially abrogated the protective efficacy of natural immunity against SARS-CoV-2 re-challenge, suggesting the importance of cellular immunity in the context of waning or subprotective antibody titers. These data demonstrate that relatively low antibody titers are sufficient for protection against SARS-CoV-2 in rhesus macaques, and that cellular immune responses may also contribute to protection if antibody responses are suboptimal. We also show that higher antibody titers are required for therapy of SARS-CoV-2 infection in macaques. These findings have important implications for the development of SARS-CoV-2 vaccines and immune-based therapeutics.