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

Oberhardt, Valerie; Luxenburger, Hendrik; Kemming, Janine; Schulien, Isabel; Ciminski, Kevin; Giese, Sebastian; Csernalabics, Benedikt; Lang-Meli, Julia; Janowska, Iga; Staniek, Julian; Wild, Katharina; Basho, Kristi; Marinescu, Mircea Stefan; Fuchs, Jonas; Topfstedt, Fernando; Janda, Ales; Sogukpinar, Oezlem; Hilger, Hanna; Stete, Katarina; Emmerich, Florian; Bengsch, Bertram; Waller, Cornelius F.; Rieg, Siegbert; Sagar; Boettler, Tobias; Zoldan, Katharina; Kochs, Georg; Schwemmle, Martin; Rizzi, Marta; Thimme, Robert; Neumann-Haefelin, Christoph; Hofmann, Maike

SARS-CoV-2 spike mRNA vaccines(1–3) mediate protection from severe disease as early as ten days after prime vaccination(3), 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.