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A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection.
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; Franken, Kees L M C; Drijfhout, Jan Wouter; Melief, Cornelis J M; Zondag, Gerben C M; Ossendorp, Ferry; Arens, Ramon.
Afiliación
  • Pardieck IN; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • van der Sluis TC; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • van der Gracht ETI; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Veerkamp DMB; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Behr FM; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • van Duikeren S; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Beyrend G; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Rip J; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Nadafi R; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Beyranvand Nejad E; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Mülling N; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Brasem DJ; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Camps MGM; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Myeni SK; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Bredenbeek PJ; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Kikkert M; Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Kim Y; Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
  • Cicin-Sain L; Department of Viral Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
  • Abdelaal T; Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
  • van Gisbergen KPJM; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
  • Franken KLMC; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands.
  • Drijfhout JW; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Melief CJM; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
  • Zondag GCM; ISA Pharmaceuticals BV, Leiden, The Netherlands.
  • Ossendorp F; Immunetune BV, Leiden, The Netherlands.
  • Arens R; Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands.
Nat Commun ; 13(1): 3966, 2022 07 08.
Article en En | MEDLINE | ID: mdl-35803932
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Epítopos de Linfocito T / COVID-19 Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Epítopos de Linfocito T / COVID-19 Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Reino Unido