{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:14:40Z","timestamp":1790378080093,"version":"4.1.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The widespread chronic enteritis known as Paratuberculosis (PTB) or Johne's disease (JD) is caused by <jats:italic>Mycobacterium avium<\/jats:italic> subspecies <jats:italic>paratuberculosis<\/jats:italic> (MAP), posing a significant threat to global public health. Given the challenges associated with PTB or JD, the development and application of vaccines are potentially important for disease control. The aim of this study was to design a multi-epitope vaccine against MAP. A total of 198 MAP genomes were analyzed using pan-genome and reverse vaccinology approaches. B-cell and T-cell epitope analysis was performed on the selected promising cross-protective antigens followed by selection of epitopes with high antigenicity, no allergenicity, and no toxicity for the design of the vaccine. The designed vaccine was evaluated through molecular dynamics simulations, molecular docking, and immunological simulations. The results revealed the identification of five promising cross-protective antigens. In total, 10 B-cell epitopes, 10 HTL epitopes, and 9 CTL epitopes were selected for the design of the vaccine. Both the vaccine candidate and the vaccine-TLR4 complex demonstrated considerable stability in molecular dynamics simulations. Molecular docking studies confirmed that the vaccine candidate successfully interacted with TLR4. Immunological simulations showed an increase in both B-cell and T-cell populations after vaccination. Additionally, the vaccine candidate exhibited a codon adaptability index of 1.0 and a GC content of 53.64%, indicating strong potential for successful expression in <jats:italic>Escherichia coli<\/jats:italic>. This research developed a multi-epitope vaccine targeting MAP through pan-genomes and reverse vaccinology methods, offering innovative strategies for creating effective vaccines against MAP.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1505313","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:42:29Z","timestamp":1738046549000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["In silico design of a multi-epitope vaccine against Mycobacterium avium subspecies paratuberculosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Weiqi","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luru","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangdong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzhang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqing","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/vr.121.7.142","article-title":"Economic losses due to paratuberculosis in dairy cattle","volume":"121","author":"Benedictus","year":"1987","journal-title":"Vet Rec"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2003.11.008","article-title":"Relationship between antibodies against Mycobacterium avium subsp. paratuberculosis in milk and shape of lactation curves","volume":"62","author":"Kudahl","year":"2004","journal-title":"Prev Vet Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.565324","article-title":"The impact of paratuberculosis on milk production, fertility, and culling in large commercial hungarian dairy herds","volume":"7","author":"Ozsvari","year":"2020","journal-title":"Front Vet Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3168\/jds.2009-2742","article-title":"Effect of Johne\u2019s disease status on reproduction and culling in dairy cattle","volume":"93","author":"Smith","year":"2010","journal-title":"J Dairy Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2005.05.011","article-title":"Effects of seropositivity for bovine leukemia virus, bovine viral diarrhoea virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum on culling in dairy cattle in four Canadian provinces","volume":"109","author":"Tiwari","year":"2005","journal-title":"Vet Microbiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.prevetmed.2012.08.006","article-title":"Herd-level prevalence of Mycobacterium avium subsp. paratuberculosis infection in United States dairy herds in 2007","volume":"108","author":"Lombard","year":"2013","journal-title":"Prev Vet Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1017\/s0022029905001007","article-title":"Economic impact of reduced milk production associated with Johne\u2019s disease on dairy operations in the USA","volume":"72","author":"Losinger","year":"2005","journal-title":"J Dairy Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/ani10010020","article-title":"Isolation of Mycobacterium avium subsp. 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