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

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.

SUBMITTER: Reinscheid M

PROVIDER: S-EPMC9358914 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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

Reinscheid Matthias M Luxenburger Hendrik H Karl Vivien V Graeser Anne A Giese Sebastian S Ciminski Kevin K Reeg David B DB Oberhardt Valerie V Roehlen Natascha N Lang-Meli Julia J Heim Kathrin K Gross Nina N Baum Christina C Rieg Siegbert S Speer Claudius C Emmerich Florian F Breisinger Susanne S Steinmann Daniel D Bengsch Bertram B Boettler Tobias T Kochs Georg G Schwemmle Martin M Thimme Robert R Neumann-Haefelin Christoph C Hofmann Maike M

Nature communications 20220808 1

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 ...[more]

PMID: 35941157

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Project description:Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells. Here we show that long-lived memory CD8 T cells are derived from a subset of effector T cells through a process of dedifferentiation. To assess the developmental origin of memory CD8 T cells, we investigated changes in DNA methylation programming at naive and effector cell-associated genes in virus-specific CD8 T cells during acute lymphocytic choriomeningitis virus infection in mice. Methylation profiling of terminal effector versus memory-precursor CD8 T cell subsets showed that, rather than retaining a naive epigenetic state, the subset of cells that gives rise to memory cells acquired de novo DNA methylation programs at naive-associated genes and became demethylated at the loci of classically defined effector molecules. Conditional deletion of the de novo methyltransferase Dnmt3a at an early stage of effector differentiation resulted in reduced methylation and faster re-expression of naive-associated genes, thereby accelerating the development of memory cells. Longitudinal phenotypic and epigenetic characterization of the memory-precursor effector subset of virus-specific CD8 T cells transferred into antigen-free mice revealed that differentiation to memory cells was coupled to erasure of de novo methylation programs and re-expression of naive-associated genes. Thus, epigenetic repression of naive-associated genes in effector CD8 T cells can be reversed in cells that develop into long-lived memory CD8 T cells while key effector genes remain demethylated, demonstrating that memory T cells arise from a subset of fate-permissive effector T cells.

Dataset Information

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

Publications

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

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