Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine
Valerie Oberhardt, Hendrik Luxenburger, Janine Kemming, Isabel Schulien, Kevin Ciminski, Sebastian Giese, Benedikt Csernalabics, Julia Lang‐Meli, Iga Janowska, Julian Staniek, Katharina Wild, Kristi Basho, Mircea Stefan Marinescu, Jonas Fuchs, Fernando Topfstedt, Aleš Janda, Oezlem Sogukpinar, Hanna Hilger, Katarina Stete, Florian Emmerich, Bertram Bengsch, Cornelius F. Waller, Siegbert Rieg, Sagar, Tobias Boettler, Katharina Zoldan, Georg Kochs, Martin Schwemmle, Marta Rizzi, Robert Thimme, Christoph Neumann‐Haefelin, Maike Hofmann
Abstract
Abstract 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.