A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection.

Pardieck, Iris N; van der Sluis, Tetje C; van der Gracht, Esmé T I; Veerkamp, Dominique M B; Behr, Felix M; van Duikeren, Suzanne; Beyrend, Guillaume; Rip, Jasper et al. · Nat Commun · 2022

basic_science · Level V

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Abstract

Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8<sup>+</sup> T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection. The third vaccine dose of the single T cell epitope peptide results in superior generation of effector-memory T cells and tissue-resident memory T cells, and these tertiary vaccine-specific CD8<sup>+</sup> T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8<sup>+</sup> effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8<sup>+</sup> T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.

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