Peters, M. Q.; Young, A. L.; Stolarczuk, J. E.; Glad, M.; Layton, E.; Logue, J. K.; Minkah, N. K.; Chu, H. Y.; Englund, J. A.; Sather, N.; Seshadri, C.; Kachikis, A.; Harrington, W. E.

BACKGROUND: Safe and effective vaccines are a key preventative measure to protect infants from SARS-CoV-2 infection and disease. Although mRNA vaccines induce robust antibody titers in infants, little is known about the quality of CD4 T-cell responses induced by vaccination. CD4 T-cell responses are important in orchestrating coordinated immune responses during infection and may help to limit disease severity. METHODS: To characterize the CD4 T-cell response to SARS-CoV-2 mRNA vaccination in infants, we sampled blood from 13 infants before and after primary SARS-CoV-2 mRNA vaccine series; samples from 12 historical vaccinated adults were used for comparisons. PBMC were stimulated with Spike peptide pools and the ability of CD4 T-cells to secrete Th1, Th2, and Th17 cytokines was quantified. A measure of polyfunctionality was generated using the COMPASS algorithm. RESULTS: We observed a significant increase in CD4 T-cells producing IL-2 (0.01% vs. 0.08%, p=0.04) and TNF- (0.007% vs. 0.07%, p=0.007) following vaccination in infants but a more muted induction of IFN-{gamma} production (0.01% vs 0.04%, p=0.08). This contrasted with adults, in whom vaccination induced robust production of IFN-{gamma}, IL-2, and TNF-. Th2 and Th17 responses were limited in both infants and adults. In infants, CD4 T-cell responses post-vaccination were greater in those who received mRNA-1273 versus BNT162b. In contrast to CD4 T-cell responses, Spike-specific IgG titers were similar in infants and adults. CONCLUSIONS: These data suggest that infants have restricted induction of cytokine producing CD4 T-cells following SARS-CoV-2 mRNA vaccination relative to adults.