Neutralizing-antibody-independent SARS-CoV-2 control correlated with intranasal-vaccine-induced CD8+ T cell responses

Cell Rep Med. 2022 Jan 19;3(2):100520. doi: 10.1016/j.xcrm.2022.100520. eCollection 2022 Feb 15.

Abstract

Effective vaccines are essential for the control of the coronavirus disease 2019 (COVID-19) pandemic. Currently developed vaccines inducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S)-antigen-specific neutralizing antibodies (NAbs) are effective, but the appearance of NAb-resistant S variant viruses is of great concern. A vaccine inducing S-independent or NAb-independent SARS-CoV-2 control may contribute to containment of these variants. Here, we investigate the efficacy of an intranasal vaccine expressing viral non-S antigens against intranasal SARS-CoV-2 challenge in cynomolgus macaques. Seven vaccinated macaques exhibit significantly reduced viral load in nasopharyngeal swabs on day 2 post-challenge compared with nine unvaccinated controls. The viral control in the absence of SARS-CoV-2-specific NAbs is significantly correlated with vaccine-induced, viral-antigen-specific CD8+ T cell responses. Our results indicate that CD8+ T cell induction by intranasal vaccination can result in NAb-independent control of SARS-CoV-2 infection, highlighting a potential of vaccine-induced CD8+ T cell responses to contribute to COVID-19 containment.

Keywords: CD8+ T cell; COVID-19; intranasal; vaccine; variant; viral vector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal / methods*
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • COVID-19 / epidemiology
  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19 Vaccines / immunology
  • Chlorocebus aethiops
  • Coronavirus Envelope Proteins / immunology
  • Coronavirus M Proteins / immunology
  • Coronavirus Nucleocapsid Proteins / immunology
  • Disease Models, Animal
  • Female
  • Macaca fascicularis
  • Male
  • Pandemics / prevention & control
  • Phosphoproteins / immunology
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology
  • Treatment Outcome
  • Vaccination / methods*
  • Vero Cells
  • Viral Load

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Coronavirus Envelope Proteins
  • Coronavirus M Proteins
  • Coronavirus Nucleocapsid Proteins
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • envelope protein, SARS-CoV-2
  • membrane protein, SARS-CoV-2
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2