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

IN Pardieck, TC van der Sluis… - Nature …, 2022 - nature.com
IN Pardieck, TC van der Sluis, ETI van der Gracht, DMB Veerkamp, FM Behr, S van Duikeren…
Nature communications, 2022nature.com
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 …
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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