Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge

English version

Autoři: Xiaoyan Zheng ^aff001; Jennifer D. Oduro ^aff001; Julia D. Boehme ^aff002; Lisa Borkner ^aff001; Thomas Ebensen ^aff001; Ulrike Heise ^aff004; Marcus Gereke ^aff002; Marina C. Pils ^aff004; Astrid Krmpotic ^aff005; Carlos A. Guzmán ^aff001; Dunja Bruder ^aff002; Luka Čičin-Šain ^aff001
Působiště autorů: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany ^aff001; Research Group Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany ^aff002; Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto von-Guericke University, Magdeburg, Germany ^aff003; Mouse Pathology Unit, Helmholtz Centre for Infection Research, Braunschweig, Germany ^aff004; Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka Croatia ^aff005; German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, Germany ^aff006
Vyšlo v časopise: Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge. PLoS Pathog 15(9): e32767. doi:10.1371/journal.ppat.1008036
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008036

Souhrn

Cytomegalovirus (CMV) is a ubiquitous β-herpesvirus that establishes life-long latent infection in a high percentage of the population worldwide. CMV induces the strongest and most durable CD8⁺ T cell response known in human clinical medicine. Due to its unique properties, the virus represents a promising candidate vaccine vector for the induction of persistent cellular immunity. To take advantage of this, we constructed a recombinant murine CMV (MCMV) expressing an MHC-I restricted epitope from influenza A virus (IAV) H1N1 within the immediate early 2 (ie2) gene. Only mice that were immunized intranasally (i.n.) were capable of controlling IAV infection, despite the greater potency of the intraperitoneally (i.p.) vaccination in inducing a systemic IAV-specific CD8⁺ T cell response. The protective capacity of the i.n. immunization was associated with its ability to induce IAV-specific tissue-resident memory CD8⁺ T (CD8T_RM) cells in the lungs. Our data demonstrate that the protective effect exerted by the i.n. immunization was critically mediated by antigen-specific CD8⁺ T cells. CD8T_RM cells promoted the induction of IFNγ and chemokines that facilitate the recruitment of antigen-specific CD8⁺ T cells to the lungs. Overall, our results showed that locally applied MCMV vectors could induce mucosal immunity at sites of entry, providing superior immune protection against respiratory infections.

Klíčová slova:

Biology and life sciences – Cell biology – Cellular types – Animal cells – Blood cells – White blood cells – T cells – Cytotoxic T cells – Immune cells – Cell motility – Chemotaxis – Chemokines – Antibodies – Organisms – Viruses – RNA viruses – Orthomyxoviruses – Influenza viruses – Influenza A virus – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Physiology – Spleen – Biochemistry – Proteins – Immune system proteins – Medicine and health sciences – Immunology – Immune response – Pathology and laboratory medicine – Pathogens – Immune physiology – Research and analysis methods – Spectrum analysis techniques – Spectrophotometry – Cytophotometry – Flow cytometry

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