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

Abstract

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-naive 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-naive 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-naive 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-naive counterparts.

ImmunosuppressiveTherapies Differently Modulate Humoral- and T-Cell-Specific Responses to COVID-19 mRNA Vaccine in Rheumatoid Arthritis Patients

“…Notably, CD4 + T-cell frequency was higher compared to that observed for the CD8 + T cells. These data agree with the results from the HCWs cohorts (5,(27)(28)(29)(30)(31) and the COVID-19 convalescent subjects (17,32). Remarkably, CD8 + T-cell response was lower in the RA cohort compared to that observed in the HCWs.…”

COVID-19 Delta Variant: Perceptions, Worries, and Vaccine-Booster Acceptability among Healthcare Workers

“…It is known that mRNA vaccines induce a robust T cell response to emerging viral variants, and that the mix and match vaccine strategy offers robust immunogenicity and tolerable reactogenicity. The HCWs who were aware of such information showed a higher willingness to receive a third booster dose [58,59].…”

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“…Investigations with pseudoviruses possessing RBD mutations carried by variants of concern demonstrated that the neutralizing activity of plasma from vaccinated individuals showed a small but significant decreases of onefold to threefold against E484K, N501Y or the K417N + E484K + N501Y triple mutant 59 . Other data indicate that the effect of N501Y alone on neutralization is relatively modest, and other studies using sera from 20 participants in a trial of the BNT162b2 vaccine showed neutralizing titres equivalent to those of pseudoviruses carrying the N501 and Y501 mutations 82 . Other investigations with recombinant viruses carrying N501Y, ΔH69–V70 + N501Y + D614G or E484K + N501Y + D614G demonstrated that compared with the Wuhan-Hu-1 reference virus, only E484K + N501Y + D614G resulted in a small and modest reduction in neutralization by postvaccination sera elicited by two BNT162b2 doses, and only modest differences in neutralization were seen compared with the Wuhan-Hu-1 reference virus 83 .…”