MAIT cell activation augments adenovirus vector vaccine immunogenicity.
| Title: | MAIT cell activation augments adenovirus vector vaccine immunogenicity. |
|---|---|
| Authors: | Provine NM; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK. nicholas.provine@ndm.ox.ac.uk paul.klenerman@ndm.ox.ac.uk.; Amini A; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Garner LC; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Spencer AJ; Jenner Institute, University of Oxford, Oxford, UK.; Dold C; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.; Hutchings C; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.; Silva Reyes L; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.; FitzPatrick MEB; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Chinnakannan S; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.; Oguti B; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.; Raymond M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.; Ulaszewska M; Jenner Institute, University of Oxford, Oxford, UK.; Troise F; Nouscom, SRL, Rome, Italy.; Ceinge Biotechnologie Avanzate, Naples, Italy.; Sharpe H; Jenner Institute, University of Oxford, Oxford, UK.; Morgan SB; Respiratory Medicine Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK.; Hinks TSC; Respiratory Medicine Unit, Nuffield Department of Medicine - Experimental Medicine, University of Oxford, Oxford, UK.; Lambe T; Jenner Institute, University of Oxford, Oxford, UK.; Capone S; ReiThera, SRL, Rome, Italy.; Folgori A; ReiThera, SRL, Rome, Italy.; Barnes E; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Jenner Institute, University of Oxford, Oxford, UK.; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK.; Rollier CS; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.; Pollard AJ; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, UK.; Klenerman P; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK. nicholas.provine@ndm.ox.ac.uk paul.klenerman@ndm.ox.ac.uk.; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK. |
| Source: | Science (New York, N.Y.) [Science] 2021 Jan 29; Vol. 371 (6528), pp. 521-526. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 0404511 Publication Model: Print Cited Medium: Internet ISSN: 1095-9203 (Electronic) Linking ISSN: 00368075 NLM ISO Abbreviation: Science Subsets: MEDLINE |
| Imprint Name(s): | Publication: : Washington, DC : American Association for the Advancement of Science; Original Publication: New York, N.Y. : [s.n.] 1880- |
| MeSH Terms: | Immunogenicity, Vaccine*; Adenoviridae/*immunology ; Mucosal-Associated Invariant T Cells/*immunology ; Viral Vaccines/*immunology; CD8-Positive T-Lymphocytes/immunology ; Dendritic Cells/immunology ; Genetic Vectors/immunology ; Interferon-alpha/metabolism ; Interleukin-18/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Animals ; Humans ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL |
| Abstract: | Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)-derived interferon (IFN)-α and monocyte-derived interleukin-18. IFN-α-induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.; (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.) |
| Comments: | Comment in: Science. 2021 Jan 29;371(6528):460-461. doi: 10.1126/science.abf8121.. (PMID: 33510011); Comment in: Nat Rev Immunol. 2021 Mar;21(3):134-135. doi: 10.1038/s41577-021-00517-y.. (PMID: 33589808) |
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| Grant Information: | MC_PC_20060 United Kingdom MRC_ Medical Research Council; 23521 United Kingdom CRUK_ Cancer Research UK; 211050/Z/18/Z United Kingdom WT_ Wellcome Trust; MR/V028448/1 United Kingdom MRC_ Medical Research Council; MC_PC_13073 United Kingdom MRC_ Medical Research Council; 109965 United Kingdom WT_ Wellcome Trust; MR/M007693/1 United Kingdom MRC_ Medical Research Council; 109965/Z/15/Z United Kingdom WT_ Wellcome Trust; 29991 United Kingdom CRUK_ Cancer Research UK; MR/R014485/1 United Kingdom MRC_ Medical Research Council |
| Substance Nomenclature: | 0 (Interferon-alpha); 0 (Interleukin-18); 0 (Tumor Necrosis Factor-alpha); 0 (Viral Vaccines) |
| Entry Date(s): | Date Created: 20210129 Date Completed: 20210226 Latest Revision: 20250530 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC7610941 |
| DOI: | 10.1126/science.aax8819 |
| PMID: | 33510029 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't