tetano
Editor, Senior Moderator
PLoS Pathog. 2019 Sep 16;15(9):e1008036. doi: 10.1371/journal.ppat.1008036. [Epub ahead of print]
[h=1]Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge.[/h] Zheng X[SUP]1[/SUP], Oduro JD[SUP]1[/SUP], Boehme JD[SUP]2,[/SUP][SUP]3[/SUP], Borkner L[SUP]1[/SUP], Ebensen T[SUP]1[/SUP], Heise U[SUP]4[/SUP], Gereke M[SUP]2,[/SUP][SUP]3[/SUP], Pils MC[SUP]4[/SUP], Krmpotic A[SUP]5[/SUP], Guzm?n CA[SUP]1[/SUP], Bruder D[SUP]2,[/SUP][SUP]3[/SUP], Čičin-?ain L[SUP]1,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h] 1 Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany. 2 Research Group Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany. 3 Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto von-Guericke University, Magdeburg, Germany. 4 Mouse Pathology Unit, Helmholtz Centre for Infection Research, Braunschweig, Germany. 5 Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka Croatia. 6 German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, Germany.
[h=3]Abstract[/h] 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.
PMID: 31525249 DOI: 10.1371/journal.ppat.1008036
[h=1]Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge.[/h] Zheng X[SUP]1[/SUP], Oduro JD[SUP]1[/SUP], Boehme JD[SUP]2,[/SUP][SUP]3[/SUP], Borkner L[SUP]1[/SUP], Ebensen T[SUP]1[/SUP], Heise U[SUP]4[/SUP], Gereke M[SUP]2,[/SUP][SUP]3[/SUP], Pils MC[SUP]4[/SUP], Krmpotic A[SUP]5[/SUP], Guzm?n CA[SUP]1[/SUP], Bruder D[SUP]2,[/SUP][SUP]3[/SUP], Čičin-?ain L[SUP]1,[/SUP][SUP]6[/SUP].
[h=3]Author information[/h] 1 Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany. 2 Research Group Immune Regulation, Helmholtz Centre for Infection Research, Braunschweig, Germany. 3 Infection Immunology Group, Institute of Medical Microbiology, Infection Control and Prevention, Health Campus Immunology, Infectiology and Inflammation, Otto von-Guericke University, Magdeburg, Germany. 4 Mouse Pathology Unit, Helmholtz Centre for Infection Research, Braunschweig, Germany. 5 Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka Croatia. 6 German Centre for Infection Research (DZIF), Partner site Hannover-Braunschweig, Germany.
[h=3]Abstract[/h] 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.
PMID: 31525249 DOI: 10.1371/journal.ppat.1008036