{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:35:42Z","timestamp":1790825742908,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["PSIA2020AGDG-3319"],"award-info":[{"award-number":["PSIA2020AGDG-3319"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The <jats:italic>Mycobacterium avium<\/jats:italic> complex (MAC)\u2014comprising <jats:italic>M. colombiense<\/jats:italic>, <jats:italic>M. avium<\/jats:italic>, and<jats:italic>M. intracellulare<\/jats:italic>\u2014is an emerging group of opportunistic pathogens responsible for significant morbidity and mortality, particularly in immunocompromised individuals. Despite this growing burden, no vaccines currently provide cross-species protection. In silico vaccine design offers a rapid, cost-effective strategy to identify immunogenic epitopes and assemble multi-epitope constructs with optimized safety and efficacy. Accordingly, we aimed to develop a candidate multi-epitope vaccine (MEV) targeting conserved antigens across multiple MAC species.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From a genomic survey of nontuberculous mycobacteria (NTM) in Zimbabwe, we assembled complete genomes for <jats:italic>M. colombiense<\/jats:italic> (MCOL), <jats:italic>M. avium<\/jats:italic> (MAV), and <jats:italic>M. intracellulare<\/jats:italic> (MINT). Using both local and global reference datasets, we screened the conserved immunodominant proteins 85A, 85B, and 85C for high-affinity T-helper lymphocyte (THL) epitopes. Promising epitopes were further evaluated for antigenicity, immunogenicity, physicochemical stability, and population coverage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Epitope mapping across the nine target proteins yielded 82 THL epitopes predicted to bind 13 MHC class II (DRB*) alleles, ensuring broad coverage within Zimbabwean and pan-African populations. Clustering analyses consolidated 26 unique epitopes into 11 consensus peptides, 65.4% of which derived from the 85B proteins. <jats:italic>In silico<\/jats:italic> immune simulations predicted robust humoral and cellular responses, including elevated IgG titers, T-helper and T-cytotoxic cell proliferation and increased secretion of IFN-\u03b3 and IL-2 following MEV administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings indicate that our construct possesses strong immunogenic potential and cross-species applicability. We present here a rationally designed MEV candidate that merits further experimental validation as a broad-spectrum vaccine against multiple MAC species.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1589083","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:29:52Z","timestamp":1749101392000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["In silico multi-epitope-based vaccine design for Mycobacterium avium complex species"],"prefix":"10.3389","volume":"16","author":[{"given":"Leah","family":"Kashiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonderful T.","family":"Choga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinashe","family":"Musasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasipanodya","family":"Nziramasanga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutendo B.","family":"Gutsire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn S.","family":"Zijenah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman L.","family":"Mukarati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simani","family":"Gaseitsiwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sikhulile","family":"Moyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyasha","family":"Chin\u2019ombe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00027","article-title":"Infection sources of a common non-tuberculous mycobacterial pathogen, mycobacterium avium complex","volume":"4","author":"Nishiuchi","year":"2017","journal-title":"Front Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.26444\/aaem\/136398","article-title":"The Mycobacterium avium complex \u2013 an underestimated threat to humans and animals","volume":"29","author":"Kaczmarkowska","year":"2022","journal-title":"Ann Agric Environ Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e48270","DOI":"10.7759\/cureus.48270","article-title":"Unveiling the clinical diversity in nontuberculous mycobacteria (NTM) infections: A comprehensive review","volume":"15","author":"Bhanushali","year":"2023","journal-title":"Cureus"},{"key":"B4","article-title":"Mycobacterium avium infections in animals. 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