{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:57:51Z","timestamp":1780574271004,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,7]],"date-time":"2021-11-07T00:00:00Z","timestamp":1636243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772147"],"award-info":[{"award-number":["81772147"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971909"],"award-info":[{"award-number":["81971909"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Mycobacterium bovis<\/jats:italic> bacillus Calmette\u2010Gu\u00e9rin (BCG) is an attenuated live vaccine that provides insufficient protection against tuberculosis (TB), the underlying mechanisms for which remain unknown. Assuming that the BCG vaccine inherits immune evasive strategies from virulent parent <jats:italic>M.\u00a0bovis<\/jats:italic> strains, we aimed to identify the associated genes and assess their effects on the vaccine efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three genes, <jats:italic>BCG_3174<\/jats:italic>, <jats:italic>BCG_1782<\/jats:italic>, and <jats:italic>BCG_2432c<\/jats:italic>, associated with immune evasion were first identified via bioinformatics analysis and then confirmed in the genome of <jats:italic>M.\u00a0bovis<\/jats:italic> and 12 commercial BCG vaccine substrains using Polymerase Chain Reaction (PCR) and DNA sequencing. These genes were disrupted to develop mutant strains, and their effects on autophagy and their protective efficacy were further compared with the BCG vaccine in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the three identified genes, only the disruption of <jats:italic>BCG_2432c<\/jats:italic>, namely \u0394BCG_2432c, conferred stronger protection against intranasal TB in vaccinated mice, when compared with the BCG vaccine. \u0394BCG_2432c showed a stronger ability to trigger intracellular ROS\u2010mediated complete autophagic flux in infected THP\u20101 cells that resulted in higher antigen presentation. The improved protection could be attributed to early and increased IFN\u2010\u03b3<jats:sup>+<\/jats:sup> CD4<jats:sup>+<\/jats:sup> T<jats:sub>EM<\/jats:sub> and IL\u20102<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T<jats:sub>CM<\/jats:sub> cells in the spleens and lungs of \u0394BCG_2432c\u2010vaccinated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The insufficient efficacy of the BCG vaccine is attributable to the important autophagy\u2010inhibition gene <jats:italic>BCG_2432c<\/jats:italic> that blocks the autophagosome\u2010lysosome pathway of antigen presentation. \u0394BCG_2432c provides a promising platform to either replace the current BCG vaccine or develop vaccines that are more effective against TB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15158","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T16:24:53Z","timestamp":1635351893000},"page":"619-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Deletion of <i>BCG_2432c<\/i> from the Bacillus Calmette\u2010Gu\u00e9rin vaccine enhances autophagy\u2010mediated immunity against tuberculosis"],"prefix":"10.1111","volume":"77","author":[{"given":"Yaqi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maopeng","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6268-5461","authenticated-orcid":false,"given":"Yandi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Human Body Anatomy School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6679-1752","authenticated-orcid":false,"given":"Qing","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banga Ndzouboukou","family":"Jo\u2010Lewis","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongjie","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-372X","authenticated-orcid":false,"given":"Xionglin","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit790"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g4643"},{"key":"e_1_2_8_5_1","volume-title":"Global Tuberculosis Report 2020","author":"World Health Organization (WHO)","year":"2020"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5419.1520"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1211"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz285"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.07.005"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.11.038"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1928"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/32183"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.059"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2012.01799.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030110"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.01049.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.182.2.377-384.2000"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001230"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120251109"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.09.003"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.2016"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122560"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.575504"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2017.09.010"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2017.07.005"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02439"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00679\u201016"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12223"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.4167\/jbv.2009.39.1.1"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100037"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3259"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737216"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100987"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13894"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3254"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30625-X"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(16)00099-0"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.15158","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/all.15158","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.15158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T12:52:06Z","timestamp":1692276726000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.15158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,7]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["10.1111\/all.15158"],"URL":"https:\/\/doi.org\/10.1111\/all.15158","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,7]]},"assertion":[{"value":"2021-05-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}