CD8 T Cells Contribute to Vaccine Protection Against SARS-CoV-2 in Macaques

Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against SARS-CoV-2 infection. Recently, robust vaccine prevention of severe disease with SARS-CoV-2 variants that largely escape NAb responses has been reported, suggesting a role for other immune parameters for virologic control. However, direct data demonstrating a role of CD8(+) T cells in vaccine protection has not yet been reported. In this study, we show that vaccine-elicited CD8(+) T cells contribute substantially to virologic control following SARS-CoV-2 challenge in rhesus macaques. We vaccinated 30 macaques with a single immunization of the adenovirus vector-based vaccine Ad26.COV2.S or sham and then challenged them with 5x10(5) TCID(50) SARS-CoV-2 B.1.617.2 (Delta) by the intranasal and intratracheal routes. All vaccinated animals were infected by this high-dose challenge but showed rapid virologic control in nasal swabs and bronchoalveolar lavage by day 4 following challenge. However, administration of an anti-CD8α or anti-CD8β depleting monoclonal antibody in vaccinated animals prior to SARS-CoV-2 challenge resulted in higher levels of peak and day 4 virus in both the upper and lower respiratory tracts. These data demonstrate that CD8(+) T cells contribute substantially to vaccine protection against SARS-CoV-2 replication in macaques.