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

SARS-CoV-2 spike mRNA vaccines^1-3 mediate protection from severe disease as early as ten days after prime vaccination³, when neutralizing antibodies are hardly detectable^4-6. Vaccine-induced CD8⁺ T cells may therefore be the main mediators of protection at this early stage^7,8. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. Here we show on a single-epitope level that a stable and fully functional CD8⁺ T cell response is vigorously mobilized one week after prime vaccination with bnt162b2, when circulating CD4⁺ T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion that generated highly differentiated effector CD8⁺ T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared with 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, are 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.