Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination

Painter, Mark M.; Mathew, Divij; Goel, Rishi R.; Apostolidis, Sokratis A.; Pattekar, Ajinkya; Kuthuru, Oliva; Baxter, Amy E.; Herati, Ramin S.; Oldridge, Derek A.; Gouma, Sigrid; Hicks, Philip; Dysinger, Sarah; Lundgreen, Kendall A.; Kuri-Cervantes, Leticia; Adamski, Sharon; Hicks, Amanda; Korte, Scott; Giles, Josephine R.; Weirick, Madison E.; McAllister, Christopher M.; Dougherty, Jeanette; Long, Sherea; D’Andrea, Kurt; Hamilton, Jacob T.; Betts, Michael R.; Bates, Paul; Hensley, Scott E.; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Greenplate, Allison R.; Wherry, E. John

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.