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, Maike Hofmann
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 3 rd and 4 th 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 3 rd vaccination. Both 4 th 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.