Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine.

SARS-CoV-2 spike mRNA vaccines1-3 mediate protection from severe disease as early as 10 days post prime vaccination3, when neutralizing antibodies are hardly detectable4-6. Vaccine-induced CD8+ T cells may thus be the main mediators of protection at this early stage7,8. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. We show on a single epitope level that a stable and fully functional CD8+ T cell response is vigorously mobilized one week after bnt162b2 prime vaccination when circulating CD4+ T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion generating highly differentiated effector CD8+ T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared to natural infection, vaccine-induced early memory T cells exhibited similar functional capacities but a different subset distribution. Our results indicate that CD8+ T cells are important effector cells, expanded in the early protection window after prime vaccination, precede maturation of other effector arms of vaccine-induced immunity and are stably maintained after boost vaccination.