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

Abstract

Effective vaccines are essential for the control of the COVID-19 pandemic. Currently-developed vaccines inducing 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 to 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.

Graphical Abstract

Abstract

Ishii et al. show neutralization-independent SARS-CoV-2 control associated with vaccine-induced CD8 ⁺ T-cell responses, indicating that virus-specific CD8 ⁺ T-cell induction by intranasal vaccination can result in SARS-CoV-2 control. Results highlight the potential of vaccine-induced CD8 ⁺ T-cell responses to contribute to the control of SARS-CoV-2 variants.