{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:42:03Z","timestamp":1789872123319,"version":"4.0.1"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T00:00:00Z","timestamp":1525219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0196815","type":"journal-article","created":{"date-parts":[[2018,5,2]],"date-time":"2018-05-02T13:54:42Z","timestamp":1525269282000},"page":"e0196815","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":25,"title":["A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5590-9666","authenticated-orcid":true,"given":"St\u00e9phane","family":"Leung-Theung-Long","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles-Antoine","family":"Coupet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Gouanvic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris","family":"Schmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huguette","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heena","family":"Soni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Converse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilibeth","family":"Arias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Kleinpeter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beno\u00eet","family":"Sansas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khisimuzi","family":"Mdluli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Vilaplana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pere-Joan","family":"Cardona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Nuermberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Baptiste","family":"Marchand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Silvestre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Inchausp\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2018,5,2]]},"reference":[{"key":"ref1","article-title":"Global tuberculosis report","year":"2016"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"16076","DOI":"10.1038\/nrdp.2016.76","article-title":"Tuberculosis","volume":"2","author":"M Pai","year":"2016","journal-title":"Nature reviews Disease primers"},{"issue":"12","key":"ref3","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1093\/cid\/ciu186","article-title":"The temporal dynamics of relapse and reinfection tuberculosis after successful treatment: a retrospective cohort study","volume":"58","author":"FM Marx","year":"2014","journal-title":"Clin Infect Dis"},{"key":"ref4","first-page":"10","article-title":"Exogenous reinfection of tuberculosis in a low-burden area","volume":"10","author":"C Schiroli","year":"2015","journal-title":"Infection"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.micpath.2012.12.002","article-title":"Vaccination against tuberculosis: how can we better BCG?","volume":"58","author":"JM Pitt","year":"2013","journal-title":"Microb Pathog"},{"key":"ref6","unstructured":"The 47th Union World Conference on Lung Health. (Communication), Liverpool, United Kingdom. 2016."},{"issue":"20","key":"ref7","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1056\/NEJMc1505196","article-title":"Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis","volume":"373","author":"GV Bloemberg","year":"2015","journal-title":"The New England journal of medicine"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3389\/fmicb.2016.00354","article-title":"The Small Breathing Amplitude at the Upper Lobes Favors the Attraction of Polymorphonuclear Neutrophils to Mycobacterium tuberculosis Lesions and Helps to Understand the Evolution toward Active Disease in An Individual-Based Model","volume":"7","author":"PJ Cardona","year":"2016","journal-title":"Frontiers in microbiology"},{"issue":"3","key":"ref9","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/MCP.0000000000000041","article-title":"Tuberculosis vaccine development at a divide","volume":"20","author":"SH Kaufmann","year":"2014","journal-title":"Current opinion in pulmonary medicine"},{"issue":"4","key":"ref10","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/joim.12031","article-title":"Shortening the 'short-course' therapy- insights into host immunity may contribute to new treatment strategies for tuberculosis","volume":"273","author":"T Schon","year":"2013","journal-title":"J Intern Med"},{"issue":"2","key":"ref11","doi-asserted-by":"crossref","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":"C Aagaard","year":"2011","journal-title":"Nat Med"},{"issue":"8","key":"ref12","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/infdis\/jis425","article-title":"Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment","volume":"207","author":"RN Coler","year":"2013","journal-title":"J Infect Dis"},{"issue":"5","key":"ref13","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.micinf.2016.03.005","article-title":"Post-exposure vaccination with the vaccine candidate Bacillus Calmette-Guerin DeltaureC::hly induces superior protection in a mouse model of subclinical tuberculosis","volume":"18","author":"M Gengenbacher","year":"2016","journal-title":"Microbes and infection"},{"issue":"8","key":"ref14","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1128\/CVI.00094-08","article-title":"Induction of a specific strong polyantigenic cellular immune response after short-term chemotherapy controls bacillary reactivation in murine and guinea pig experimental models of tuberculosis","volume":"15","author":"E Guirado","year":"2008","journal-title":"Clinical and vaccine immunology: CVI"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ijid.2017.01.030","article-title":"Experimental animal modelling for TB vaccine development","volume":"56","author":"PJ Cardona","year":"2017","journal-title":"International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases"},{"issue":"1","key":"ref16","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ni.3048","article-title":"The balance between protective and pathogenic immune responses in the TB-infected lung","volume":"16","author":"IM Orme","year":"2015","journal-title":"Nat Immunol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/bs.aivir.2016.07.001","article-title":"Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development","volume":"97","author":"A Volz","year":"2017","journal-title":"Advances in virus research"},{"issue":"12","key":"ref18","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.4161\/hv.21689","article-title":"Therapeutic vaccination to treat chronic infectious diseases: current clinical developments using MVA-based vaccines","volume":"8","author":"H Boukhebza","year":"2012","journal-title":"Hum Vaccin Immunother"},{"issue":"11","key":"ref19","doi-asserted-by":"crossref","first-page":"e0143552","DOI":"10.1371\/journal.pone.0143552","article-title":"A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates","volume":"10","author":"S Leung-Theung-Long","year":"2015","journal-title":"PLoS One"},{"issue":"34","key":"ref20","doi-asserted-by":"crossref","first-page":"29993","DOI":"10.1074\/jbc.M111.248732","article-title":"Solution structure of the Mycobacterium tuberculosis EsxG.EsxH complex: functional implications and comparisons with other M. tuberculosis Esx family complexes","volume":"286","author":"D Ilghari","year":"2011","journal-title":"The Journal of biological chemistry"},{"key":"ref21","article-title":"Translating 2A Research into Practice, Innovations in Biotechnology","author":"GA Luke","year":"2012"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1128\/JVI.60.2.436-449.1986","article-title":"Conserved TAAATG sequence at the transcriptional and translational initiation sites of vaccinia virus late genes deduced by structural and functional analysis of the HindIII H genome fragment","volume":"60","author":"JL Rosel","year":"1986","journal-title":"Journal of virology"},{"issue":"6","key":"ref23","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.2144\/97236st07","article-title":"Compact, synthetic, vaccinia virus early\/late promoter for protein expression","volume":"23","author":"S Chakrabarti","year":"1997","journal-title":"BioTechniques"},{"issue":"1","key":"ref24","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1128\/JVI.54.1.30-37.1985","article-title":"In vitro mutagenesis of the promoter region for a vaccinia virus gene: evidence for tandem early and late regulatory signals","volume":"54","author":"MA Cochran","year":"1985","journal-title":"Journal of virology"},{"issue":"2","key":"ref25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/CVI.00678-13","article-title":"Immunological characterization of a modified vaccinia virus Ankara vector expressing the human papillomavirus 16 E1 protein","volume":"21","author":"C Remy-Ziller","year":"2014","journal-title":"Clin Vaccine Immunol"},{"key":"ref26","first-page":"397","article-title":"Genetic immunization and comprehensive screening approaches in HLA-A2 transgenic mice lead to the identification of three novel epitopes in hepatitis C virus NS3 antigen","author":"P Martin","journal-title":"Journal of medical virology"},{"issue":"8","key":"ref27","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1128\/AAC.00912-12","article-title":"Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis","volume":"56","author":"IM Rosenthal","year":"2012","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"7","key":"ref28","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1128\/AAC.00105-15","article-title":"Evaluation of moxifloxacin-containing regimens in pathologically distinct murine tuberculosis models","volume":"59","author":"SY Li","year":"2015","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"11","key":"ref29","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/j.vaccine.2004.09.008","article-title":"Immunotherapy with fragmented Mycobacterium tuberculosis cells increases the effectiveness of chemotherapy against a chronical infection in a murine model of tuberculosis","volume":"23","author":"PJ Cardona","year":"2005","journal-title":"Vaccine"},{"issue":"12","key":"ref30","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nrmicro2236","article-title":"The spectrum of latent tuberculosis: rethinking the biology and intervention strategies","volume":"7","author":"CE Barry 3rd","year":"2009","journal-title":"Nat Rev Microbiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"37793","DOI":"10.1038\/srep37793","article-title":"New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles","volume":"6","author":"M Coppola","year":"2016","journal-title":"Scientific reports"},{"issue":"6","key":"ref32","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1084\/jem.178.6.2243","article-title":"Disseminated tuberculosis in interferon gamma gene-disrupted mice","volume":"178","author":"AM Cooper","year":"1993","journal-title":"J Exp Med"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.TBTB2-0034-2017","article-title":"Preclinical Efficacy Testing of New Drug Candidates","volume":"5","author":"EL Nuermberger","year":"2017","journal-title":"Microbiology spectrum"},{"issue":"1","key":"ref34","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1053\/j.gastro.2014.03.007","article-title":"Efficacy of immunotherapy with TG4040, peg-interferon, and ribavirin in a Phase 2 study of patients with chronic HCV infection","volume":"147","author":"AM Di Bisceglie","year":"2014","journal-title":"Gastroenterology"},{"issue":"2","key":"ref35","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S1470-2045(15)00483-0","article-title":"TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b\/3 trial","volume":"17","author":"E Quoix","year":"2016","journal-title":"The Lancet Oncology"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"688","DOI":"10.3389\/fimmu.2017.00688","article-title":"Applying Precision Medicine and Immunotherapy Advances from Oncology to Host-Directed Therapies for Infectious Diseases","volume":"8","author":"RN Mahon","year":"2017","journal-title":"Frontiers in immunology"},{"key":"ref37","first-page":"37","article-title":"Immunotherapy for tuberculosis: future prospects","volume":"5","author":"G Abate","year":"2016","journal-title":"ImmunoTargets and therapy"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.3389\/fmicb.2016.01536","article-title":"The Progress of Therapeutic Vaccination with Regard to Tuberculosis","volume":"7","author":"PJ Cardona","year":"2016","journal-title":"Frontiers in microbiology"},{"issue":"4","key":"ref39","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1016\/S1473-3099(16)00078-5","article-title":"Host-directed therapies for infectious diseases: current status, recent progress, and future prospects","volume":"16","author":"A Zumla","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"ref40","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1046\/j.1440-1711.2000.00936.x","article-title":"Role of CD8 T cells in mycobacterial infections","volume":"78","author":"SM Smith","year":"2000","journal-title":"Immunology and cell biology"},{"issue":"4","key":"ref41","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1615\/CritRevImmunol.v26.i4.30","article-title":"Mycobacterium tuberculosis-specific CD8+ T cells and their role in immunity","volume":"26","author":"JS Woodworth","year":"2006","journal-title":"Crit Rev Immunol"},{"issue":"2","key":"ref42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00430-012-0278-6","article-title":"Targeting multidrug-resistant tuberculosis (MDR-TB) by therapeutic vaccines","volume":"202","author":"SA Prabowo","year":"2013","journal-title":"Medical microbiology and immunology"},{"issue":"1","key":"ref43","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1128\/AAC.01691-15","article-title":"Contribution of Oxazolidinones to the Efficacy of Novel Regimens Containing Bedaquiline and Pretomanid in a Mouse Model of Tuberculosis","volume":"60","author":"R Tasneen","year":"2015","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"6","key":"ref44","doi-asserted-by":"crossref","first-page":"3114","DOI":"10.1128\/AAC.00384-12","article-title":"Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis","volume":"56","author":"K Williams","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"ref45","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.jmii.2014.03.005","article-title":"Recombinant tuberculosis vaccine AEC\/BC02 induces antigen-specific cellular responses in mice and protects guinea pigs in a model of latent infection","volume":"48","author":"JB Lu","year":"2015","journal-title":"Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.coi.2017.07.008","article-title":"Tuberculosis vaccines\u2014perspectives from the NIH\/NIAID Mycobacteria vaccine testing program","volume":"47","author":"AA Izzo","year":"2017","journal-title":"Current opinion in immunology"},{"issue":"11","key":"ref47","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1038\/ni.1792","article-title":"Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands","volume":"10","author":"R Barbalat","year":"2009","journal-title":"Nature immunology"},{"issue":"6","key":"ref48","doi-asserted-by":"crossref","first-page":"e1000480","DOI":"10.1371\/journal.ppat.1000480","article-title":"Innate immune sensing of modified vaccinia virus Ankara (MVA) is mediated by TLR2-TLR6, MDA-5 and the NALP3 inflammasome","volume":"5","author":"J Delaloye","year":"2009","journal-title":"PLoS pathogens"},{"issue":"2","key":"ref49","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1182\/blood-2006-06-027136","article-title":"Innate immunity against vaccinia virus is mediated by TLR2 and requires TLR-independent production of IFN-beta","volume":"109","author":"J Zhu","year":"2007","journal-title":"Blood"},{"issue":"5","key":"ref50","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.4049\/jimmunol.1302523","article-title":"A novel murine cytomegalovirus vaccine vector protects against Mycobacterium tuberculosis","volume":"193","author":"PC Beverley","year":"2014","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"39","key":"ref51","doi-asserted-by":"crossref","first-page":"4241","DOI":"10.1016\/j.vaccine.2013.03.020","article-title":"Clinical development of Modified Vaccinia virus Ankara vaccines","volume":"31","author":"SC Gilbert","year":"2013","journal-title":"Vaccine"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fimmu.2013.00128","article-title":"Prime-boost strategies in mucosal immunization affect local IgA production and the type of th response","volume":"4","author":"F Fiorino","year":"2013","journal-title":"Frontiers in immunology"},{"issue":"1","key":"ref53","doi-asserted-by":"crossref","first-page":"8322","DOI":"10.1038\/s41598-017-08665-9","article-title":"Enhancing Immune Responses to Cancer Vaccines Using Multi-Site Injections","volume":"7","author":"RC Mould","year":"2017","journal-title":"Scientific reports"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0196815","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T07:59:26Z","timestamp":1604217566000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0196815"}},"subtitle":[],"editor":[{"given":"Angelo A.","family":"Izzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2018,5,2]]},"references-count":53,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0196815","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,2]]}}}