Authors: Mark M. Painter, Divij Mathew, Rishi R. Goel, Sokratis A. Apostolidis, Ajinkya Pattekar, Oliva Kuthuru, Amy E. Baxter, Ramin S. Herati, Derek A. Oldridge, Sigrid Gouma, Philip Hicks, Sarah Dysinger, Kendall A. Lundgreen, Leticia Kuri-Cervantes, Sharon Adamski, Amanda Hicks, Scott Korte, Josephine R. Giles, Madison E. Weirick, Christopher M. McAllister, Jeanette Dougherty, Sherea Long, Kurt D’Andrea, Jacob T. Hamilton, Michael R. Betts, Paul Bates, Scott E. Hensley, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Allison R. Greenplate, E. John Wherry
Summary: SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2 naïve and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naïve subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cell and neutralizing antibody, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2 naïve and recovered individuals. Lastly, whereas booster vaccination improved T cell responses in SARS-CoV-2 naïve subjects, the second dose had little effect in SARS-CoV-2 recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2 naïve individuals.
Source: Immunity, 2021