A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection
Iris N. Pardieck (Leiden University Medical Center)
Tetje C. van der Sluis (Leiden University Medical Center)
Esmé T.I. van der Gracht (Leiden University Medical Center)
Dominique M.B. Veerkamp (Leiden University Medical Center)
Felix M. Behr (Leiden University Medical Center)
Suzanne van Duikeren (Leiden University Medical Center)
Guillaume Beyrend (Leiden University Medical Center)
Jasper Rip (Leiden University Medical Center)
Tamim Abdelaal (Leiden University Medical Center, TU Delft - Pattern Recognition and Bioinformatics)
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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+ 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+ T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8+ effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8+ T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.
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