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

SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early as ten days after prime vaccination, when neutralizing antibodies are hardly detectable. Vaccine-induced CD8 T cells may therefore be the main mediators of protection at this early stage. 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.