CD8 T cells contribute to vaccine protection against SARS-CoV-2 in macaques
Jinyan Liu, Jingyou Yu, Katherine McMahan, Catherine Jacob-Dolan, Xuan He, Victoria Giffin, Cindy Wu, Michaela Sciacca, Olivia Powers, Felix Nampanya, Jessica Miller, Michelle A. Lifton, David Hope, Kevin Hall, Nicole P. Hachmann, Benjamin Chung, Tochi Anioke, Wenjun Li, Jeanne Muench, Adrienne J Gamblin, Mona Boursiquot, Anthony Cook, Mark G. Lewis, Hanné Andersen, Dan H. Barouch
Abstract
Spike-specific neutralizing antibodies (NAbs) are generally considered key correlates of vaccine protection against severe acute respiratory syndrome coronavirus 2 (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 have not yet been reported. In this study, we show that vaccine-elicited CD8 + T cells contribute substantially to virologic control after 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 5 × 10 5 median tissue culture infectious dose 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 after challenge. However, administration of an anti-CD8α– or anti-CD8β–depleting monoclonal antibody in vaccinated animals before 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.