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

Author

Listed:
  • 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
    Leiden University Medical Center)

  • 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)

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.

Suggested Citation

  • 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 Beyranvan, 2022. "A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31721-6
    DOI: 10.1038/s41467-022-31721-6
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