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

Nature. 2021 Feb;590(7847):630-634. doi: 10.1038/s41586-020-03041-6. Epub 2020 Dec 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • COVID-19 / therapy*
  • COVID-19 / virology
  • COVID-19 Serotherapy
  • Disease Models, Animal*
  • Female
  • Immunization, Passive
  • Immunoglobulin G / administration & dosage
  • Immunoglobulin G / analysis
  • Immunoglobulin G / immunology
  • Macaca mulatta / immunology
  • Macaca mulatta / virology
  • Male
  • Regression Analysis
  • SARS-CoV-2 / immunology*
  • Viral Load / immunology


  • Immunoglobulin G