Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination
Mark M Painter,
Rishi R Goel,
Sokratis A. Apostolidis,
Amy E. Baxter,
Ramin Sedaghat Herati,
Derek A. Oldridge,
Kendall A Lundgreen,
Josephine R. Giles,
Madison E. Weirick,
Christopher M. McAllister,
Jacob T. Hamilton,
Michael R. Betts,
Scott E. Hensley,
Allison R. Greenplate,
E John Wherry
Posted 22 Apr 2021
bioRxiv DOI: 10.1101/2021.04.21.440862
Posted 22 Apr 2021
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 naive 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.
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