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

Autor: 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, Nadafi, Reza, Beyranvand Nejad, Elham, Mülling, Nils, Brasem, Dena J., Camps, Marcel G. M., Myeni, Sebenzile K., Bredenbeek, Peter J., Kikkert, Marjolein, Kim, Yeonsu, Cicin-Sain, Luka, Abdelaal, Tamim, van Gisbergen, Klaas P. J. M.
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Zdroj: Nature Communications; 7/8/2022, Vol. 13 Issue 1, p1-11, 11p
Abstrakt: 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. Vaccination regimens and the number of doses required for optimal immunity and protection are critical factors in the translation of vaccines. Here the authors show administration of a three dose protocol of a single T cell epitope to the SARS-CoV-2 spike protein induces a robust CD8+ T cell response and confers protection in a lethal murine challenge model of infection. [ABSTRACT FROM AUTHOR]
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