mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status

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 and altered the phenotypic properties of
SARS-CoV-2-specific T cells, while in convalescents the second dose
changed 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
emerging viral 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.