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

Nature, 2021, vol. 597, issue 7875, 268-273

Abstract: Abstract SARS-CoV-2 spike mRNA vaccines1–3 mediate protection from severe disease as early as ten days after prime vaccination3, when neutralizing antibodies are hardly detectable4–6. Vaccine-induced CD8+ T cells may therefore 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. 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.

Date: 2021
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DOI: 10.1038/s41586-021-03841-4

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