Subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques

PLoS Pathog. 2021 Jul 19;17(7):e1009668. doi: 10.1371/journal.ppat.1009668. eCollection 2021 Jul.

Abstract

SARS-CoV-2 infection presents clinical manifestations ranging from asymptomatic to fatal respiratory failure. Despite the induction of functional SARS-CoV-2-specific CD8+ T-cell responses in convalescent individuals, the role of virus-specific CD8+ T-cell responses in the control of SARS-CoV-2 replication remains unknown. In the present study, we show that subacute SARS-CoV-2 replication can be controlled in the absence of CD8+ T cells in cynomolgus macaques. Eight macaques were intranasally inoculated with 105 or 106 TCID50 of SARS-CoV-2, and three of the eight macaques were treated with a monoclonal anti-CD8 antibody on days 5 and 7 post-infection. In these three macaques, CD8+ T cells were undetectable on day 7 and thereafter, while virus-specific CD8+ T-cell responses were induced in the remaining five untreated animals. Viral RNA was detected in nasopharyngeal swabs for 10-17 days post-infection in all macaques, and the kinetics of viral RNA levels in pharyngeal swabs and plasma neutralizing antibody titers were comparable between the anti-CD8 antibody treated and untreated animals. SARS-CoV-2 RNA was detected in the pharyngeal mucosa and/or retropharyngeal lymph node obtained at necropsy on day 21 in two of the untreated group but undetectable in all macaques treated with anti-CD8 antibody. CD8+ T-cell responses may contribute to viral control in SARS-CoV-2 infection, but our results indicate possible containment of subacute viral replication in the absence of CD8+ T cells, implying that CD8+ T-cell dysfunction may not solely lead to viral control failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / immunology
  • COVID-19 / veterinary*
  • COVID-19 / virology
  • Disease Models, Animal
  • Female
  • Humans
  • Kinetics
  • Lymphocyte Depletion / veterinary
  • Macaca fascicularis / immunology*
  • Macaca fascicularis / virology*
  • Male
  • Monkey Diseases / immunology*
  • Monkey Diseases / virology*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • SARS-CoV-2 / genetics
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology*
  • Virus Replication / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • RNA, Viral

Grants and funding

This study was supported by Research Programs from Japan Agency for Medical Research and Development (AMED) (JP19fk0108104 to AK-T; JP20nk0101601, JP21fk0410035, JP21fk0108125, JP21jk0210002 to TM) and by JSPS Grants-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan (21H02745 to TM]). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.