The BNT162b2 mRNA vaccine induces polyfunctional T cell responses with features of longevity

Guerrera, Gisella; Picozza, Mario; D’Orso, Silvia; Placido, Roberta; Pirronello, Marta; Verdiani, Alice; Termine, Andrea; Fabrizio, Carlo; Giannessi, Flavia; Sambucci, Manolo; Balice, Maria Pia; Caltagirone, Carlo; Salvia, Antonino; Rossini, Angelo; Battistini, Luca; Borsellino, Giovanna

Vaccination against SARS-CoV-2 infection has shown to be effective in preventing hospitalization for severe COVID-19. However, multiple reports of break-through infections and of waning antibody titers have raised concerns on the durability of the vaccine, and current discussions on vaccination strategies are centered on evaluating the opportunity of a third dose administration. Here, we monitored T cell responses to the Spike protein of SARS-CoV-2 in 71 healthy donors vaccinated with the Pfizer–BioNTech mRNA vaccine (BNT162b2) for up to 6 months after vaccination. We find that vaccination induces the development of a sustained anti-viral memory T cell response which includes both the CD4+ and the CD8+ lymphocyte subsets. These lymphocytes display markers of polyfunctionality, are fit for interaction with cognate cells, show features of memory stemness, and survive in significant numbers the physiological contraction of the immune response. Collectively, this data shows that vaccination with BNT162b2 elicits an immunologically competent and potentially long-lived SARS-CoV-2-specific T cell population. Understanding the immune responses to BNT162b2 provides insights on the immunological basis of the clinical efficacy of the current vaccination campaign and may instruct future vaccination strategies.