Rapid induction of antigen-specific CD4+ T cells guides 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

The 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 in healthy individuals following mRNA vaccination. Vaccination induced rapid near-maximal antigen-specific CD4+ T cell responses in all subjects after the first vaccine dose. CD8+ T cell responses developed gradually after the first and second dose and were variable. Vaccine-induced T cells had central memory characteristics and included both Tfh and Th1 subsets, similar to natural infection. Th1 and Tfh responses following the first dose predicted post-boost CD8+ T cell and neutralizing antibody levels, respectively. Integrated analysis of 26 antigen-specific T cell and humoral responses revealed coordinated features of the immune response to vaccination. Lastly, whereas booster vaccination improved CD4+ and CD8+ T cell responses in SARS-CoV-2 naïve subjects, the second vaccine dose had little effect on T cell responses in SARS-CoV-2 recovered individuals. Thus, longitudinal analysis revealed robust T cell responses to mRNA vaccination and highlighted early induction of antigen-specific CD4+ T cells. Graphical Abstract