{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:21:30Z","timestamp":1793146890058,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001509","name":"Royal Society of New Zealand Marsden Fund","doi-asserted-by":"publisher","award":["24-VUW-152"],"award-info":[{"award-number":["24-VUW-152"]}],"id":[{"id":"10.13039\/501100001509","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Mucosal-associated invariant T (MAIT) cells exist in high numbers in the body and have a unique and highly conserved T cell receptor (TCR). They can be activated in a TCR-dependent manner by ligands presented on the monomorphic protein MHC class I-related protein 1 (MR1) which is found on many cell types, including professional antigen presenting cells (APCs) and epithelial cells. This has sparked interest in the potential to exploit the MR1-MAIT cell axis for the development of vaccines against infectious disease. Within this context an MR1 ligand, typically 5-(2-oxopropylideneamino)-d-ribitylaminouracil (5-OP-RU), is administered with or without a Toll-like receptor (TLR) ligand or cytokine in a pan vaccination approach that would prime the immune response to provide protection against a variety of bacterial and viral pathogens. This strategy has led to enhanced protection in murine models of Legionella longbeachae, Francisella tularensis, Klebsiella pneumoniae, Streptococcus pneumoniae and influenza infection. However, studies against Mycobacterium tuberculosis infection have proven less successful. The second vaccination approach involves pairing the MR1 ligand with more conventional antigens that could activate CD4+ and\/or CD8+ T cells. This approach has been successful in murine models of cholera, influenza, and SARS-CoV-2, including in the context of subunit vaccines. However, there are several challenges when using MR1-MAIT cell-mediated vaccine adjuvants. These include the inherent instability of 5-OP-RU and the need for more advanced studies to better understand how the use of MR1 ligands would translate to applications in humans. This review will discuss these aspects and highlight the mechanistic studies that have been undertaken to understand how MAIT cells might elicit their effects within the context of MAIT cell-mediated vaccines for infectious disease.<\/jats:p>","DOI":"10.3390\/vaccines14020117","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T15:48:30Z","timestamp":1769442510000},"page":"117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting the MR1-MAIT Cell Axis for Vaccination Against Infectious Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-0729","authenticated-orcid":false,"given":"Mattie S. M.","family":"Timmer","sequence":"first","affiliation":[{"name":"School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington 6012, New Zealand"},{"name":"Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3882-8765","authenticated-orcid":false,"given":"Lisa M.","family":"Connor","sequence":"additional","affiliation":[{"name":"Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand"},{"name":"Malaghan Institute of Medical Research, Wellington 6242, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget L.","family":"Stocker","sequence":"additional","affiliation":[{"name":"School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington 6012, New Zealand"},{"name":"Centre for Biodiscovery, Victoria University of Wellington, Wellington 6012, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1084\/jem.178.1.1","article-title":"Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8-alpha\/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain","volume":"178","author":"Porcelli","year":"1993","journal-title":"J. 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