In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 6 ( 2023-6-29), p. e1011485-
Abstract:
Mucosa-associated invariant T (MAIT) cells are MR1-restricted, innate-like T lymphocytes with tremendous antibacterial and immunomodulatory functions. Additionally, MAIT cells sense and respond to viral infections in an MR1-independent fashion. However, whether they can be directly targeted in immunization strategies against viral pathogens is unclear. We addressed this question in multiple wild-type and genetically altered but clinically relevant mouse strains using several vaccine platforms against influenza viruses, poxviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a riboflavin-based MR1 ligand of bacterial origin, can synergize with viral vaccines to expand MAIT cells in multiple tissues, reprogram them towards a pro-inflammatory MAIT1 phenotype, license them to bolster virus-specific CD8 + T cell responses, and potentiate heterosubtypic anti-influenza protection. Repeated 5-OP-RU administration did not render MAIT cells anergic, thus allowing for its inclusion in prime-boost immunization protocols. Mechanistically, tissue MAIT cell accumulation was due to their robust proliferation, as opposed to altered migratory behavior, and required viral vaccine replication competency and Toll-like receptor 3 and type I interferon receptor signaling. The observed phenomenon was reproducible in female and male mice, and in both young and old animals. It could also be recapitulated in a human cell culture system in which peripheral blood mononuclear cells were exposed to replicating virions and 5-OP-RU. In conclusion, although viruses and virus-based vaccines are devoid of the riboflavin biosynthesis machinery that supplies MR1 ligands, targeting MR1 enhances the efficacy of vaccine-elicited antiviral immunity. We propose 5-OP-RU as a non-classic but potent and versatile vaccine adjuvant against respiratory viruses.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011485
DOI:
10.1371/journal.ppat.1011485.g001
DOI:
10.1371/journal.ppat.1011485.g002
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10.1371/journal.ppat.1011485.g003
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10.1371/journal.ppat.1011485.g004
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10.1371/journal.ppat.1011485.g005
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10.1371/journal.ppat.1011485.g006
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10.1371/journal.ppat.1011485.g007
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10.1371/journal.ppat.1011485.g008
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10.1371/journal.ppat.1011485.g009
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10.1371/journal.ppat.1011485.g010
DOI:
10.1371/journal.ppat.1011485.g011
DOI:
10.1371/journal.ppat.1011485.g012
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10.1371/journal.ppat.1011485.s001
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10.1371/journal.ppat.1011485.s002
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10.1371/journal.ppat.1011485.s003
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10.1371/journal.ppat.1011485.s004
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10.1371/journal.ppat.1011485.s005
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10.1371/journal.ppat.1011485.s006
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10.1371/journal.ppat.1011485.s007
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10.1371/journal.ppat.1011485.s008
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10.1371/journal.ppat.1011485.s009
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10.1371/journal.ppat.1011485.s010
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10.1371/journal.ppat.1011485.s011
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10.1371/journal.ppat.1011485.s012
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10.1371/journal.ppat.1011485.s013
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10.1371/journal.ppat.1011485.s014
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10.1371/journal.ppat.1011485.s015
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10.1371/journal.ppat.1011485.s016
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10.1371/journal.ppat.1011485.s017
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10.1371/journal.ppat.1011485.s018
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10.1371/journal.ppat.1011485.s019
DOI:
10.1371/journal.ppat.1011485.s020
DOI:
10.1371/journal.ppat.1011485.s021
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10.1371/journal.ppat.1011485.s022
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10.1371/journal.ppat.1011485.s023
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10.1371/journal.ppat.1011485.s024
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10.1371/journal.ppat.1011485.s025
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10.1371/journal.ppat.1011485.s026
DOI:
10.1371/journal.ppat.1011485.s027
DOI:
10.1371/journal.ppat.1011485.s028
DOI:
10.1371/journal.ppat.1011485.s029
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1