{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:01:49Z","timestamp":1790744509337,"version":"4.1.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Mycobacterium tuberculosis (Mtb)<\/jats:italic>\n                      infects approximately one-quarter of the global population, of whom 5%\u201310% develop active tuberculosis (TB). Although Bacillus Calmette\u2013Gu\u00e9rin (BCG) remains the cornerstone vaccine against severe infant TB, its efficacy in adults is limited, underscoring the need for novel TB vaccines. This study aimed to design a multi-epitope vaccine, tMEV, and validate its protective potential through bioinformatic prediction and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>tMEV was constructed from dominant T- and B-cell epitopes derived from Mtb ESAT-6, PE35, PPE38, and PE4 proteins, fused with an adjuvant. Its vaccine candidacy was assessed via physicochemical and solubility profiling, secondary and tertiary structure modeling, TLR-4 molecular docking, molecular dynamics simulation, and immune simulation. The tMEV coding sequence was cloned into pMV361 and transformed into BCG to generate recombinant BCG (rBCG-tMEV). Immunogenicity, antigenicity, and protective efficacy were evaluated in mouse immunization and Mtb challenge models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      tMEV exhibited favorable vaccine-like properties\n                      <jats:italic>in silico<\/jats:italic>\n                      . In mice, both tMEV and rBCG-tMEV induced Mtb-specific immune responses. Compared with PBS, tMEV significantly enhanced cellular and humoral immunity with a Th2-biased profile. Relative to conventional BCG, rBCG-tMEV elicited a superior mixed Th1\u2013Th2 response and higher antigen-specific immunity, accompanied by increased secretion of IFN-\u03b3, IL-2, TNF-\u03b1, granzyme B, and perforin. Moreover, rBCG-tMEV markedly reduced bacterial loads in the lungs and spleens of Mtb-infected mice, conferring partial protection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that tMEV and rBCG-tMEV possess robust immunogenicity and protective potential against Mtb, representing promising novel TB vaccine candidates and providing a rationale for future vaccine development and optimization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1912983","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:53:37Z","timestamp":1790744017000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunogenicity and protective efficacy of recombinant BCG expressing a multi-epitope vaccine against mycobacterium tuberculosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xuan-ji","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-rui","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-ting","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-long","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second People\u2019s Hospital of Kashgar Prefecture","place":["Kashgar, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-jie","family":"Zhu","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Center, The First Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-15254-8","article-title":"Rational design of a multi-epitope vaccine against Salmonella typhi via subtractive proteomics, reverse vaccinology and molecular modeling","volume":"15","author":"Albutti","year":"2025","journal-title":"Sci. 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