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

Painter, M. M.; Mathew, D.; Goel, R. R.; Apostolidis, S. A.; Pattekar, A.; Kuthuru, O.; Baxter, A. E.; Herati, R. S.; Oldridge, D. A.; Gouma, S.; Hicks, P.; Dysinger, S.; Lundgreen, K. A.; Kuri-Cervantes, L.; Adamski, S.; Hicks, A.; Korte, S.; Giles, J. R.; Weirick, M. E.; McAllister, C. M.; Dougherty, J.; Long, S.; D'Andrea, K.; Hamilton, J. T.; Betts, M. R.; Bates, P.; Hensley, S. E.; Grifoni, A.; Weiskopf, D.; Sette, A.; Greenplate, A. R.; Wherry, E. J.

doi:10.1101/2021.04.21.440862

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bioRxiv · 10.1101/2021.04.21.440862

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

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Abstract

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. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/440862v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@db812dorg.highwire.dtl.DTLVardef@fdc549org.highwire.dtl.DTLVardef@a34663org.highwire.dtl.DTLVardef@1621e52_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Painter, M. M., Mathew, D., Goel, R. R., Apostolidis, S. A., Pattekar, A., Kuthuru, O., Baxter, A. E., Herati, R. S., Oldridge, D. A., Gouma, S., Hicks, P., Dysinger, S., Lundgreen, K. A., Kuri-Cervantes, L., Adamski, S., Hicks, A., Korte, S., Giles, J. R., Weirick, M. E., McAllister, C. M., Dougherty, J., Long, S., D'Andrea, K., Hamilton, J. T., Betts, M. R., Bates, P., Hensley, S. E., Grifoni, A., Weiskopf, D., Sette, A., Greenplate, A. R., Wherry, E. J.. 2021-04-22. Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination. https://doi.org/10.1101/2021.04.21.440862

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