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


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 (CD8TRM) 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. CD8TRM 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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