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

Iris N. Pardieck, Tetje C. van der Sluis, Esmé T. I. van der Gracht, Dominique M. B. Veerkamp, Felix M. Behr, Suzanne van Duikeren, Guillaume Beyrend, Jasper Rip, Reza Nadafi, Elham Beyranvand Nejad, Nils Mülling, Dena J. Brasem, Marcel G. M. Camps, Sebenzile K. Myeni, Peter J. Bredenbeek, Marjolein Kikkert, Yeonsu Kim, Luka Cicin-Sain, Tamim Abdelaal, Klaas P. J. M. van Gisbergen, Kees L. M. C. Franken, Jan Wouter Drijfhout, Cornelis J. M. Melief, Gerben C. M. Zondag, Ferry Ossendorp and Ramon Arens ()
Additional contact information
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
Reza Nadafi: Leiden University Medical Center
Elham Beyranvand Nejad: Leiden University Medical Center
Nils Mülling: Leiden University Medical Center
Dena J. Brasem: Leiden University Medical Center
Marcel G. M. Camps: Leiden University Medical Center
Sebenzile K. Myeni: Leiden University Medical Center
Peter J. Bredenbeek: Leiden University Medical Center
Marjolein Kikkert: Leiden University Medical Center
Yeonsu Kim: Helmholtz Centre for Infection Research
Luka Cicin-Sain: Helmholtz Centre for Infection Research
Tamim Abdelaal: Delft University of Technology
Klaas P. J. M. van Gisbergen: Sanquin Research and Landsteiner Laboratory
Kees L. M. C. Franken: Leiden University Medical Center
Jan Wouter Drijfhout: Leiden University Medical Center
Cornelis J. M. Melief: ISA Pharmaceuticals BV
Gerben C. M. Zondag: Immunetune BV
Ferry Ossendorp: Leiden University Medical Center
Ramon Arens: Leiden University Medical Center

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31721-6

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