{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:11:23Z","timestamp":1787026283521,"version":"build-2736575974"},"reference-count":42,"publisher":"Frontiers Media SA","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-106559"],"award-info":[{"award-number":["MOP-106559"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"DOI":"10.3389\/fcimb.2017.00226","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T23:48:50Z","timestamp":1496188130000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Immunogenicity and Protective Efficacy of a Fusion Protein Tuberculosis Vaccine Combining Five Esx Family Proteins"],"prefix":"10.3389","volume":"7","author":[{"given":"Zhi-hao","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-feng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-zeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-tao","family":"Mai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-xiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-yan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,5,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/nm.2285","article-title":"A multistage tuberculosis vaccine that confers efficient protection before and after exposure","volume":"17","author":"Aagaard","year":"2011","journal-title":"Nat. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nrmicro1773","article-title":"Type VII secretion\u2013mycobacteria show the way","volume":"5","author":"Abdallah","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1111\/j.1365-2958.2009.06783.x","article-title":"PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5","volume":"73","author":"Abdallah","year":"2009","journal-title":"Mol. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"a018523","DOI":"10.1101\/cshperspect.a018523","article-title":"Novel vaccination strategies against tuberculosis","volume":"4","author":"Andersen","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/S0962-8479(96)90029-5","article-title":"T-cell response to mycobacterial proteins: a comparative study of tuberculous and control immunoblots of Mycobacterium tuberculosis and M. bovis BCG","volume":"77","author":"Bassey","year":"1996","journal-title":"Tuber. Lung Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"53r","DOI":"10.1126\/scitranslmed.3001094","article-title":"A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis","volume":"2","author":"Bertholet","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/503469e","article-title":"TB vaccine failure was predictable","volume":"503","author":"Beverley","year":"2013","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e1000507","DOI":"10.1371\/journal.ppat.1000507","article-title":"Systematic genetic nomenclature for type VII secretion systems","volume":"5","author":"Bitter","year":"2009","journal-title":"PLoS Pathog."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/S0140-6736(02)08353-8","article-title":"BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies","volume":"359","author":"Black","year":"2002","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1128\/IAI.57.10.3123-3130.1989","article-title":"Cloning, sequence determination, and expression of a 32-kilodalton-protein gene of Mycobacterium tuberculosis","volume":"57","author":"Borremans","year":"1989","journal-title":"Infect. Immun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1128\/IAI.68.2.791-795.2000","article-title":"ESAT-6 subunit vaccination against Mycobacterium tuberculosis","volume":"68","author":"Brandt","year":"2000","journal-title":"Infect. Immun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"S64","DOI":"10.1086\/314072","article-title":"Preventing tuberculosis with bacillus Calmette-Guerin vaccine: a meta-analysis of the literature","volume":"31","author":"Brewer","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1086\/421468","article-title":"Enhanced protection against tuberculosis by vaccination with recombinant Mycobacterium microti vaccine that induces T cell immunity against region of difference 1 antigens","volume":"190","author":"Brodin","year":"2004","journal-title":"J. Infect. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/31159","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence","volume":"393","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"B15","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.4049\/jimmunol.161.5.2356","article-title":"Molecular cloning and immunologic reactivity of a novel low molecular mass antigen of Mycobacterium tuberculosis","volume":"161","author":"Coler","year":"1998","journal-title":"J. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.4049\/jimmunol.1201593","article-title":"An unbiased genome-wide Mycobacterium tuberculosis gene expression approach to discover antigens targeted by human T cells expressed during pulmonary infection","volume":"190","author":"Commandeur","year":"2013","journal-title":"J. Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev.immunol.021908.132703","article-title":"Cell-mediated immune responses in tuberculosis","volume":"27","author":"Cooper","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1084\/jem.178.6.2243","article-title":"Disseminated tuberculosis in interferon gamma gene-disrupted mice","volume":"178","author":"Cooper","year":"1993","journal-title":"J. Exp. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/nm1592","article-title":"Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major","volume":"13","author":"Darrah","year":"2007","journal-title":"Nat. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"6332","DOI":"10.4049\/jimmunol.174.10.6332","article-title":"Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy","volume":"174","author":"Dietrich","year":"2005","journal-title":"J. Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1084\/jem.178.6.2249","article-title":"An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection","volume":"178","author":"Flynn","year":"1993","journal-title":"J. Exp. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"RESEARCH0044","DOI":"10.1186\/gb-2001-2-10-research0044","article-title":"The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria","volume":"2","author":"Gey Van Pittius","year":"2001","journal-title":"Genome Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1056\/NEJM199612263352604","article-title":"Interferon-gamma-receptor deficiency in an infant with fatal bacille Calmette-Guerin infection","volume":"335","author":"Jouanguy","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/S1473-3099(11)70146-3","article-title":"Fact and fiction in tuberculosis vaccine research: 10 years later","volume":"11","author":"Kaufmann","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"8047","DOI":"10.4049\/jimmunol.0801592","article-title":"Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells","volume":"182","author":"Lindenstrom","year":"2009","journal-title":"J. Immunol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"12434","DOI":"10.1073\/pnas.0703510104","article-title":"Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis","volume":"104","author":"Mittrucker","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1056\/NEJM199612263352602","article-title":"A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection","volume":"335","author":"Newport","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1146\/annurev.immunol.22.012703.104635","article-title":"Immunity to tuberculosis","volume":"22","author":"North","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nrmicro3230","article-title":"In search of a new paradigm for protective immunity to TB","volume":"12","author":"Nunes-Alves","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/S0966-842X(02)02345-4","article-title":"The ESAT-6\/WXG100 superfamily \u2013 and a new Gram-positive secretion system?","volume":"10","author":"Pallen","year":"2002","journal-title":"Trends Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e89313","DOI":"10.1371\/journal.pone.0089313","article-title":"WXG100 protein superfamily consists of three subfamilies and exhibits an alpha-helical C-terminal conserved residue pattern","volume":"9","author":"Poulsen","year":"2014","journal-title":"PLoS ONE"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1038\/sj.emboj.7600732","article-title":"Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6","volume":"24","author":"Renshaw","year":"2005","journal-title":"EMBO J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"21598","DOI":"10.1074\/jbc.M201625200","article-title":"Conclusive evidence that the major T-cell antigens of the Mycobacterium tuberculosis complex ESAT-6 and CFP-10 form a tight, 1:1 complex and characterization of the structural properties of ESAT-6, CFP-10, and the ESAT-6*CFP-10 complex. Implications for pathogenesis and virulence","volume":"277","author":"Renshaw","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: implications for vaccine design","volume":"8","author":"Seder","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"6340","DOI":"10.1128\/JB.00756-09","article-title":"Characterization of a Mycobacterium tuberculosis ESX-3 conditional mutant: essentiality and rescue by iron and zinc","volume":"191","author":"Serafini","year":"2009","journal-title":"J. Bacteriol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e01073","DOI":"10.1128\/mBio.01073-14","article-title":"Mycobacterial Esx-3 requires multiple components for iron acquisition","volume":"5","author":"Siegrist","year":"2014","journal-title":"MBio"},{"key":"B37","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nrmicro1419","article-title":"Advances in tuberculosis vaccine strategies","volume":"4","author":"Skeiky","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1128\/IAI.68.1.214-220.2000","article-title":"Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens","volume":"68","author":"Skjot","year":"2000","journal-title":"Infect. Immun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3569","DOI":"10.4049\/jimmunol.180.5.3569","article-title":"Bacillus Calmette-Guerin vaccination of human newborns induces T cells with complex cytokine and phenotypic profiles","volume":"180","author":"Soares","year":"2008","journal-title":"J. Immunol."},{"key":"B40","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1128\/IAI.63.5.1710-1717.1995","article-title":"Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis","volume":"63","author":"Sorensen","year":"1995","journal-title":"Infect. Immun."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S0140-6736(13)60177-4","article-title":"Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial","volume":"381","author":"Tameris","year":"2013","journal-title":"Lancet"},{"key":"B42","first-page":"181","article-title":"Revised BCG vaccination guidelines for infants at risk for HIV infection","volume":"82","year":"2007","journal-title":"Wkly. Epidemiol. Rec."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fcimb.2017.00226\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T16:39:36Z","timestamp":1692808776000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fcimb.2017.00226\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,31]]},"references-count":42,"alternative-id":["10.3389\/fcimb.2017.00226"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2017.00226","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,31]]},"article-number":"226"}}