COVID-19 mRNA booster vaccine induces transient CD8+ T effector cell responses while conserving the memory pool for subsequent reactivation

Matthias Reinscheid, Hendrik Luxenburger, Vivien Karl, Anne Graeser, Sebastian Giese, Kevin Ciminski, David B. Reeg, Valerie Oberhardt, Natascha Roehlen, Julia Lang-Meli, Kathrin Heim, Nina Gross, Christina Baum, Siegbert Rieg, Claudius Speer, Florian Emmerich, Susanne Breisinger, Daniel Steinmann, Bertram Bengsch, Tobias Boettler, Georg Kochs, Martin Schwemmle, Robert Thimme (), Christoph Neumann-Haefelin () and Maike Hofmann ()
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Matthias Reinscheid: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Hendrik Luxenburger: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Vivien Karl: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Anne Graeser: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Sebastian Giese: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Kevin Ciminski: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
David B. Reeg: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Valerie Oberhardt: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Natascha Roehlen: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Julia Lang-Meli: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Kathrin Heim: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Nina Gross: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Christina Baum: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Siegbert Rieg: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Claudius Speer: University of Heidelberg
Florian Emmerich: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Susanne Breisinger: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Daniel Steinmann: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Bertram Bengsch: Freiburg University Medical Center, Faculty of Medicine, University of Freiburg
Tobias Boettler: 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
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 Communications, 2022, vol. 13, issue 1, 1-11

Abstract: Abstract Immunization with two mRNA vaccine doses elicits robust spike-specific CD8+ T cell responses, but reports of waning immunity after COVID-19 vaccination prompt the introduction of booster vaccination campaigns. However, the effect of mRNA booster vaccination on the spike-specific CD8+ T cell response remains unclear. Here we show that spike-specific CD8+ T cells are activated and expanded in all analyzed individuals receiving the 3rd and 4th mRNA vaccine shots. This CD8+ T cell boost response is followed by a contraction phase and lasts only for about 30-60 days. The spike-specific CD8+ T memory stem cell pool is not affected by the 3rd vaccination. Both 4th vaccination and breakthrough infections with Delta and Omicron rapidly reactivate CD8+ T memory cells. In contrast, neutralizing antibody responses display little boost effect towards Omicron. Thus, COVID-19 mRNA booster vaccination elicits a transient T effector cell response while long-term spike-specific CD8+ T cell immunity is conserved to mount robust memory recall targeting emerging variants of concern.

Date: 2022
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DOI: 10.1038/s41467-022-32324-x

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