PT - JOURNAL ARTICLE AU - Jason Neidleman AU - Xiaoyu Luo AU - Matthew McGregor AU - Guorui Xie AU - Victoria Murray AU - Warner C. Greene AU - Sulggi A. Lee AU - Nadia R. Roan TI - mRNA vaccine-induced SARS-CoV-2-specific T cells recognize B.1.1.7 and B.1.351 variants but differ in longevity and homing properties depending on prior infection status AID - 10.1101/2021.05.12.443888 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.05.12.443888 4099 - http://biorxiv.org/content/early/2021/05/12/2021.05.12.443888.short 4100 - http://biorxiv.org/content/early/2021/05/12/2021.05.12.443888.full AB - While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, and whether they protect against variants. Focusing on the T cell response, we conducted a longitudinal study of infection-naïve and COVID-19 convalescent donors before vaccination and after their first and second vaccine doses, using a high-parameter CyTOF analysis to phenotype their SARS-CoV-2-specific T cells. Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity but not quality of the T cell response, while in convalescents the second dose helped neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx. These results provide reassurance that vaccine-elicited T cells respond robustly to the B.1.1.7 and B.1.351 variants, confirm that convalescents may not need a second vaccine dose, and suggest that vaccinated convalescents may have more persistent nasopharynx-homing SARS-CoV-2- specific T cells compared to their infection-naïve counterparts.SUMMARY BULLET POINTSmRNA vaccine-elicited T cells respond identically to B.1.1.7 and B.1.351 spikeSecond mRNA dose affects quantity but not quality of vaccine-elicited T cellsConvalescents’ spike CD4 T cells express more CD127 and lung-homing receptorsSpike CD4 T cell levels in blood inversely correlate with tissue migration markersBRIEF SUMMARY Neidleman et al. conducted CyTOF on antigen-specific T cells in longitudinal samples from infection-naïve and COVID-19 convalescent mRNA vaccinees. Vaccine-elicited T cells respond identically to variants, and change in quantity but not quality after first dose. Convalescents’ T cells preferentially express the longevity-associated marker CD127 and respiratory tract homing receptors.Competing Interest StatementThe authors have declared no competing interest.