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Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge.
Zheng, Xiaoyan Oduro, Jennifer D Boehme, Julia D Borkner, Lisa Ebensen, Thomas Heise, Ulrike Gereke, Marcus Pils, Marina C Krmpotic, Astrid Guzmán, Carlos A
Zheng, Xiaoyan
Oduro, Jennifer D
Boehme, Julia D
Borkner, Lisa
Ebensen, Thomas
Heise, Ulrike
Gereke, Marcus
Pils, Marina C
Krmpotic, Astrid
Guzmán, Carlos A
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2019-09-01
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Abstract
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.
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PLoS Pathog. 2019 Sep 16;15(9):e1008036. doi: 10.1371/journal.ppat.1008036. eCollection 2019 Sep.
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en
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1553-7374
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Attribution-NonCommercial-ShareAlike 4.0 International