{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T02:04:26Z","timestamp":1778724266027,"version":"3.51.4"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T00:00:00Z","timestamp":1432166400000},"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.0127907","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T13:58:29Z","timestamp":1432216709000},"page":"e0127907","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunogenicity without Efficacy of an Adenoviral Tuberculosis Vaccine in a Stringent Mouse Model for Immunotherapy during Treatment"],"prefix":"10.1371","volume":"10","author":[{"given":"S. Anisah","family":"Alyahya","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott T.","family":"Nolan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cara M. R.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Bishai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerald","family":"Sadoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gyanu","family":"Lamichhane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,5,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"e54587","DOI":"10.1371\/journal.pone.0054587","article-title":"What is the Cost of Diagnosis and Management of Drug Resistant Tuberculosis in South Africa?","volume":"8","author":"A Pooran","year":"2013","journal-title":"PLoS ONE"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.4049\/jimmunol.175.2.1107","article-title":"Long-Term Control of Mycobacterium tuberculosis Infection Is Mediated by Dynamic Immune Responses","volume":"175","author":"V Lazarevic","year":"2005","journal-title":"J Immunol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.4049\/jimmunol.1101122","article-title":"Functional Capacity of Mycobacterium tuberculosis-Specific T Cell Responses in Humans Is Associated with Mycobacterial Load","volume":"187","author":"CL Day","year":"2011","journal-title":"J Immunol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/sj.gene.6364392","article-title":"Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis","volume":"8","author":"FF Weichold","year":"2007","journal-title":"Genes Immun"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/0264-410X(93)90354-Z","article-title":"Of postulates and peccadilloes: Robert Koch and vaccine (tuberculin) therapy for tuberculosis","volume":"11","author":"DS Burke","year":"1993","journal-title":"Vaccine"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1016\/j.vaccine.2014.03.047","article-title":"Therapeutic vaccines for tuberculosis\u2014A systematic review","volume":"32","author":"MI Gr\u00f6schel","year":"2014","journal-title":"Vaccine"},{"key":"ref7","doi-asserted-by":"crossref","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":"MD Tameris","year":"2013","journal-title":"The Lancet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nrmicro3230","article-title":"In search of a new paradigm for protective immunity to TB","volume":"12","author":"C Nunes-Alves","year":"2014","journal-title":"Nat Rev Microbiol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1086\/313891","article-title":"Treatment of Latent Tuberculosis Infection: Renewed Opportunity for Tuberculosis Control","volume":"31","author":"DL Cohn","year":"2000","journal-title":"Clin Infect Dis"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"4105","DOI":"10.1128\/IAI.00004-07","article-title":"Protective Immune Responses to a Recombinant Adenovirus Type 35 Tuberculosis Vaccine in Two Mouse Strains: CD4 and CD8 T-Cell Epitope Mapping and Role of Gamma Interferon","volume":"75","author":"K Rado\u0161evi\u0107","year":"2007","journal-title":"Infect Immun"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"5908","DOI":"10.1016\/j.vaccine.2014.09.001","article-title":"The novel tuberculosis vaccine, AERAS-402, is safe in healthy infants previously vaccinated with BCG, and induces dose-dependent CD4 and CD8T cell responses","volume":"32","author":"BMN Kagina","year":"2014","journal-title":"Vaccine"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1164\/rccm.200904-0611OC","article-title":"Addition of PNU-100480 to First-Line Drugs Shortens the Time Needed to Cure Murine Tuberculosis","volume":"180","author":"KN Williams","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1055\/s-0028-1085705","article-title":"Using Animal Models to Develop New Treatments for Tuberculosis","volume":"29","author":"E Nuermberger","year":"2008","journal-title":"Semin Respir Crit Care Med"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1128\/AAC.05293-11","article-title":"Sterilizing Activity of Novel TMC207- and PA-824-Containing Regimens in a Murine Model of Tuberculosis","volume":"55","author":"R Tasneen","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.micinf.2005.08.014","article-title":"Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type","volume":"8","author":"O Gil","year":"2006","journal-title":"Microbes Infect"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1128\/IAI.71.1.483-493.2003","article-title":"Mapping of Murine Th1 Helper T-Cell Epitopes of Mycolyl Transferases Ag85A, Ag85B, and Ag85C from Mycobacterium tuberculosis","volume":"71","author":"S D\u2019Souza","year":"2003","journal-title":"Infect Immun"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.4049\/jimmunol.171.3.1602","article-title":"Enhanced Immunogenicity and Protective Efficacy Against Mycobacterium tuberculosis of Bacille Calmette-Gu\u00e9rin Vaccine Using Mucosal Administration and Boosting with a Recombinant Modified Vaccinia Virus Ankara","volume":"171","author":"NP Goonetilleke","year":"2003","journal-title":"J Immunol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e1002063","DOI":"10.1371\/journal.ppat.1002063","article-title":"Suboptimal Activation of Antigen-Specific CD4+ Effector Cells Enables Persistence of M. tuberculosis In Vivo","volume":"7","author":"TD Bold","year":"2011","journal-title":"PLoS Pathog"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1002\/1521-4141(200012)30:12<3689::AID-IMMU3689>3.0.CO;2-4","article-title":"Control of latent Mycobacterium tuberculosis infection is dependent on CD8 T cells","volume":"30","author":"LAH Van Pinxteren","year":"2000","journal-title":"Eur J Immunol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"e1000392","DOI":"10.1371\/journal.ppat.1000392","article-title":"A Critical Role for CD8 T Cells in a Nonhuman Primate Model of Tuberculosis","volume":"5","author":"CY Chen","year":"2009","journal-title":"PLoS Pathog"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.4049\/jimmunol.1003304","article-title":"CD4 T Cells Promote Rather than Control Tuberculosis in the Absence of PD-1\u2013Mediated Inhibition","volume":"186","author":"DL Barber","year":"2011","journal-title":"J Immunol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.4049\/jimmunol.1400676","article-title":"Aerosol Vaccination with AERAS-402 Elicits Robust Cellular Immune Responses in the Lungs of Rhesus Macaques but Fails To Protect against High-Dose Mycobacterium tuberculosis Challenge","volume":"193","author":"PA Darrah","year":"2014","journal-title":"J Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1164\/rccm.201003-0334OC","article-title":"Specific T Cell Frequency and Cytokine Expression Profile Do Not Correlate with Protection against Tuberculosis after Bacillus Calmette-Gu\u00e9rin Vaccination of Newborns","volume":"182","author":"BMN Kagina","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.immuni.2011.03.022","article-title":"Intravital Imaging Reveals Limited Antigen Presentation and T Cell Effector Function in Mycobacterial Granulomas","volume":"34","author":"JG Egen","year":"2011","journal-title":"Immunity"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1002\/eji.201344358","article-title":"High-frequency vaccine-induced CD8+ T cells specific for an epitope naturally processed during infection with Mycobacterium tuberculosis do not confer protection","volume":"44","author":"T Lindenstr\u00f8m","year":"2014","journal-title":"Eur J Immunol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1164\/rccm.201006-0974OC","article-title":"Negative and Positive Predictive Value of a Whole-Blood Interferon-\u03b3 Release Assay for Developing Active Tuberculosis","volume":"183","author":"R Diel","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: implications for vaccine design","volume":"8","author":"RA Seder","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"6311","DOI":"10.4049\/jimmunol.1300248","article-title":"Control of Chronic Mycobacterium tuberculosis Infection by CD4 KLRG1\u2212 IL-2\u2013Secreting Central Memory Cells","volume":"190","author":"T Lindenstr\u00f8m","year":"2013","journal-title":"J Immunol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1189\/jlb.1204723","article-title":"Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection","volume":"77","author":"M Gonzalez-Juarrero","year":"2005","journal-title":"J Leukoc Biol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"e1003805","DOI":"10.1371\/journal.ppat.1003805","article-title":"iNKT Cell Production of GM-CSF Controls Mycobacterium tuberculosis","volume":"10","author":"AC Rothchild","year":"2014","journal-title":"PLoS Pathog"},{"key":"ref31","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"},{"key":"ref32","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"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/sj.gt.3302418","article-title":"Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efficient form of treatment for tuberculosis in mice","volume":"12","author":"CL Silva","year":"2004","journal-title":"Gene Ther"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1164\/rccm.200904-0536OC","article-title":"Shortening Treatment in Adults with Noncavitary Tuberculosis and 2-Month Culture Conversion","volume":"180","author":"JL Johnson","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"e249","DOI":"10.1371\/journal.pmed.0020249","article-title":"Preclinical Assessment of HIV Vaccines and Microbicides by Repeated Low-Dose Virus Challenges","volume":"2","author":"RR Regoes","year":"2005","journal-title":"PLoS Med"},{"key":"ref36","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":"J Cardona P-","year":"2005","journal-title":"Vaccine"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1128\/AAC.47.3.833-836.2003","article-title":"Mycobacterium tuberculosis in the Extracellular Compartment: an Underestimated Adversary","volume":"47","author":"J Grosset","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.tube.2013.07.004","article-title":"A new unifying theory of the pathogenesis of","volume":"94","author":"IM Orme","year":"2014","journal-title":"Tuberculosis"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"e17550","DOI":"10.1371\/journal.pone.0017550","article-title":"Location of Intra- and Extracellular M. tuberculosis Populations in Lungs of Mice and Guinea Pigs during Disease Progression and after Drug Treatment","volume":"6","author":"DR Hoff","year":"2011","journal-title":"PLoS ONE"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/ng.590","article-title":"Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved","volume":"42","author":"I Comas","year":"2010","journal-title":"Nat Genet"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1099\/vir.0.81956-0","article-title":"Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells","volume":"87","author":"M Havenga","year":"2006","journal-title":"J Gen Virol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1128\/JVI.02696-06","article-title":"Comparative Seroprevalence and Immunogenicity of Six Rare Serotype Recombinant Adenovirus Vaccine Vectors from Subgroups B and D","volume":"81","author":"P Abbink","year":"2007","journal-title":"J Virol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0127907","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T09:45:56Z","timestamp":1540287956000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0127907"}},"subtitle":[],"editor":[{"given":"Mauricio Martins","family":"Rodrigues","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,5,21]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,5,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0127907","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,21]]}}}