{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T12:49:47Z","timestamp":1777898987020,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"National Key Research and Development Project of China","doi-asserted-by":"publisher","award":["2021YFC2301500"],"award-info":[{"award-number":["2021YFC2301500"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Committee of Science and Technology","award":["24490713600"],"award-info":[{"award-number":["24490713600"]}]},{"name":"Shanghai Committee of Science and Technology","award":["ZD2021CY001"],"award-info":[{"award-number":["ZD2021CY001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Tuberculosis (TB) remains a major global health challenge, highlighting the urgent need for more effective vaccines. This study aimed to develop an artificial intelligence-guided epitope prediction and prioritization pipeline to identify immunodominant peptides from Mycobacterium tuberculosis (Mtb) and to evaluate the immunogenicity and protective efficacy of the resulting vaccine candidates. Methods: An AI-guided framework was used to predict and prioritize immunodominant Mtb epitopes, leading to the generation of 72 recombinant immunogens. Among these, RI-13, RI-20, and RI-31 were selected as the leading candidates. Their protective efficacy was assessed in a zebrafish TB infection model and in BALB\/c mice following DNA vaccination. Humoral and cellular immune responses were further evaluated in C57BL\/6 mice. Results: RI-13, RI-20, and RI-31 markedly reduced infection-associated pathology and lowered bacterial burden by up to 1.5 log10 in the zebrafish TB infection model, outperforming benchmark antigen combinations, including the Ag85A plus ESAT6\/CFP10 cocktail used in the phase III vaccine candidate GamTBvac. In BALB\/c mice, DNA vaccination with each construct reduced pulmonary mycobacterial burden by approximately 0.3 log10 and alleviated lung tissue damage. In addition, all three candidates elicited robust humoral and cellular immune responses, with RI-13 showing the strongest overall immunogenicity and inducing a balanced Th1, Th2, and Th17 response profile in C57BL\/6 mice. Conclusions: These findings identify RI-13, derived from Rv1174c, as a promising next-generation TB vaccine candidate. More broadly, this study supports the utility of an AI-guided framework for the rational design and preclinical prioritization of novel TB immunogens.<\/jats:p>","DOI":"10.3390\/vaccines14050408","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:33:17Z","timestamp":1777627997000},"page":"408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recombinant Immunogens Designed by AI Epitope Prioritization Confer Protection Against Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Ning","family":"Fang","sequence":"first","affiliation":[{"name":"Shanghai Pudong Hospital and School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anke","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Pudong Hospital and School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhifei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Pudong Hospital and School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menglin","family":"Ye","sequence":"additional","affiliation":[{"name":"Shanghai Pudong Hospital and School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiasong","family":"Pan","sequence":"additional","affiliation":[{"name":"Shanghai Pudong Hospital and School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weili","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1742-7460","authenticated-orcid":false,"given":"Decheng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Basic Medical Sciences, China Three Gorges University, Yichang 443002, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8490-4389","authenticated-orcid":false,"given":"Zhidong","family":"Hu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-3559","authenticated-orcid":false,"given":"Xiaoyong","family":"Fan","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Infectious Diseases and Biosecurity, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8422-4594","authenticated-orcid":false,"given":"Bingdong","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Immunology, Shanghai Jiao Tong University, Shanghai 200025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoping","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4858-0361","authenticated-orcid":false,"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-3175","authenticated-orcid":false,"given":"Jixi","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Pudong Hospital and School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai 200438, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.tube.2015.05.017","article-title":"Tuberculosis: A disease without boundaries","volume":"95","author":"Fogel","year":"2015","journal-title":"Tuberculosis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.2106\/JBJS.RVW.18.00035","article-title":"Spinal Tuberculosis: A Literature Review","volume":"7","author":"Ali","year":"2019","journal-title":"JBJS Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/S0140-6736(25)02433-X","article-title":"Global tuberculosis response off track: Urgent priorities to end the world\u2019s top infectious 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