{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T17:17:27Z","timestamp":1769015847982,"version":"3.49.0"},"reference-count":100,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Development of a vaccine against pulmonary tuberculosis may require immunization strategies that induce a high frequency of Ag-specific CD4 and CD8 T cells in the lung. The nonhuman primate model is essential for testing such approaches because it has predictive value for how vaccines elicit responses in humans. In this study, we used an aerosol vaccination strategy to administer AERAS-402, a replication-defective recombinant adenovirus (rAd) type 35 expressing Mycobacterium tuberculosis Ags Ag85A, Ag85B, and TB10.4, in bacillus Calmette\u2013Gu\u00e9rin (BCG)-primed or unprimed rhesus macaques. Immunization with BCG generated low purified protein derivative\u2013specific CD4 T cell responses in blood and bronchoalveolar lavage. In contrast, aerosolized AERAS-402 alone or following BCG induced potent and stable Ag85A\/b-specific CD4 and CD8 effector T cells in bronchoalveolar lavage that largely produced IFN-\u03b3, as well as TNF and IL-2. Such responses induced by BCG, AERAS-402, or both failed to confer overall protection following challenge with 275 CFUs M. tuberculosis Erdman, although vaccine-induced responses associated with reduced pathology were observed in some animals. Anamnestic T cell responses to Ag85A\/b were not detected in blood of immunized animals after challenge. Overall, our data suggest that a high M. tuberculosis challenge dose may be a critical factor in limiting vaccine efficacy in this model. However, the ability of aerosol rAd immunization to generate potent cellular immunity in the lung suggests that using different or more immunogens, alternative rAd serotypes with enhanced immunogenicity, and a physiological challenge dose may achieve protection against M. tuberculosis.<\/jats:p>","DOI":"10.4049\/jimmunol.1400676","type":"journal-article","created":{"date-parts":[[2014,7,15]],"date-time":"2014-07-15T04:13:20Z","timestamp":1405397600000},"page":"1799-1811","source":"Crossref","is-referenced-by-count":88,"title":["Aerosol Vaccination with AERAS-402 Elicits Robust Cellular Immune Responses in the Lungs of Rhesus Macaques but Fails To Protect against High-Dose <i>Mycobacterium tuberculosis<\/i> Challenge"],"prefix":"10.1093","volume":"193","author":[{"given":"Patricia A","family":"Darrah","sequence":"first","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane L","family":"Bolton","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A","family":"Lackner","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepak","family":"Kaushal","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pyone Pyone","family":"Aye","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smriti","family":"Mehra","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J","family":"Didier","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad J","family":"Roy","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center , Covington, LA 70433"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Srinivas S","family":"Rao","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Hokey","sequence":"additional","affiliation":[{"name":"Aeras , Rockville, MD 20850"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles A","family":"Scanga","sequence":"additional","affiliation":[{"name":"Aeras , Rockville, MD 20850"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donata R","family":"Sizemore","sequence":"additional","affiliation":[{"name":"Aeras , Rockville, MD 20850"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerald C","family":"Sadoff","sequence":"additional","affiliation":[{"name":"Aeras , Rockville, MD 20850"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Roederer","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A","family":"Seder","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,8,15]]},"reference":[{"key":"2025030707295843900_r1","volume-title":"Global Tuberculosis Report 2013.","author":"World Health Organization","year":"2013"},{"key":"2025030707295843900_r2","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1038\/35021239","article-title":"Vaccines against intracellular infections requiring cellular immunity","volume":"406","author":"Seder","year":"2000","journal-title":"Nature"},{"key":"2025030707295843900_r3","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.immuni.2010.09.015","article-title":"Future vaccination strategies against tuberculosis: thinking outside the box","volume":"33","author":"Kaufmann","year":"2010","journal-title":"Immunity"},{"key":"2025030707295843900_r4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1542\/peds.96.1.29","article-title":"The efficacy of bacillus Calmette-Gu\u00e9rin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature","volume":"96","author":"Colditz","year":"1995","journal-title":"Pediatrics"},{"key":"2025030707295843900_r5","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0140-6736(95)92348-9","article-title":"Variation in protection by BCG: implications of and for heterologous immunity","volume":"346","author":"Fine","year":"1995","journal-title":"Lancet"},{"key":"2025030707295843900_r6","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1586\/erv.12.94","article-title":"Prime-boost approaches to tuberculosis vaccine development","volume":"11","author":"Dalmia","year":"2012","journal-title":"Expert Rev. Vaccines"},{"key":"2025030707295843900_r7","doi-asserted-by":"crossref","first-page":"e1002607","DOI":"10.1371\/journal.ppat.1002607","article-title":"Vaccines against tuberculosis: where are we and where do we need to go?","volume":"8","author":"Ottenhoff","year":"2012","journal-title":"PLoS Pathog."},{"key":"2025030707295843900_r8","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1128\/IAI.70.8.4501-4509.2002","article-title":"Dissemination of Mycobacterium tuberculosis is influenced by host factors and precedes the initiation of T-cell immunity","volume":"70","author":"Chackerian","year":"2002","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r9","doi-asserted-by":"crossref","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":"2025030707295843900_r10","doi-asserted-by":"crossref","first-page":"10961","DOI":"10.1073\/pnas.0801496105","article-title":"ESAT-6-specific CD4 T cell responses to aerosol Mycobacterium tuberculosis infection are initiated in the mediastinal lymph nodes","volume":"105","author":"Reiley","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707295843900_r11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1084\/jem.20071367","article-title":"Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs","volume":"205","author":"Wolf","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030707295843900_r12","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.4049\/jimmunol.144.10.3980","article-title":"Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells","volume":"144","author":"Allan","year":"1990","journal-title":"J. Immunol."},{"key":"2025030707295843900_r13","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1084\/jem.20050265","article-title":"Properties and protective value of the secondary versus primary T helper type 1 response to airborne Mycobacterium tuberculosis infection in mice","volume":"201","author":"Jung","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025030707295843900_r14","doi-asserted-by":"crossref","first-page":"4320","DOI":"10.1128\/IAI.69.7.4320-4328.2001","article-title":"CD8+ T cells participate in the memory immune response to Mycobacterium tuberculosis","volume":"69","author":"Serbina","year":"2001","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r15","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1002\/eji.200940279","article-title":"A key role for lung-resident memory lymphocytes in protective immune responses after BCG vaccination","volume":"40","author":"Connor","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"2025030707295843900_r16","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/mi.2012.19","article-title":"Mechanisms of delayed anti-tuberculosis protection in the lung of parenteral BCG-vaccinated hosts: a critical role of airway luminal T cells","volume":"5","author":"Horvath","year":"2012","journal-title":"Mucosal Immunol."},{"key":"2025030707295843900_r17","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1084\/jem.20080353","article-title":"Delayed protection by ESAT-6-specific effector CD4+ T cells after airborne M. tuberculosis infection","volume":"205","author":"Gallegos","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030707295843900_r18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/978-1-4614-6111-1_14","article-title":"Immunization strategies against pulmonary tuberculosis: considerations of T cell geography","volume":"783","author":"Horvath","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"2025030707295843900_r19","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/mi.2011.45","article-title":"Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge","volume":"5","author":"Bolton","year":"2012","journal-title":"Mucosal Immunol."},{"key":"2025030707295843900_r20","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/nri3251","article-title":"Recent progress in mucosal vaccine development: potential and limitations","volume":"12","author":"Lycke","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"2025030707295843900_r21","doi-asserted-by":"crossref","first-page":"22213","DOI":"10.1073\/pnas.1015536108","article-title":"Genetic immunization in the lung induces potent local and systemic immune responses","volume":"107","author":"Song","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707295843900_r22","first-page":"351","article-title":"Protection of monkeys against airborne tuberculosis by aerosol vaccination with bacillus Calmette-Gu\u00e9rin","volume":"107","author":"Barclay","year":"1973","journal-title":"Am. Rev. Respir. Dis."},{"key":"2025030707295843900_r23","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1128\/IAI.72.1.238-246.2004","article-title":"Single intranasal mucosal Mycobacterium bovis BCG vaccination confers improved protection compared to subcutaneous vaccination against pulmonary tuberculosis","volume":"72","author":"Chen","year":"2004","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r24","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1073\/pnas.0800043105","article-title":"Immunization by a bacterial aerosol","volume":"105","author":"Garcia-Contreras","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707295843900_r25","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0192-0561(94)90033-7","article-title":"BCG-induced mucosal immune responses","volume":"16","author":"Gheorghiu","year":"1994","journal-title":"Int. J. Immunopharmacol."},{"key":"2025030707295843900_r26","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jinf.2005.12.017","article-title":"Protective efficacy of intranasal vaccination with Mycobacterium bovis BCG against airway Mycobacterium tuberculosis challenge in mice","volume":"53","author":"Giri","year":"2006","journal-title":"J. Infect."},{"key":"2025030707295843900_r27","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":"Goonetilleke","year":"2003","journal-title":"J. Immunol."},{"key":"2025030707295843900_r28","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":"Abbink","year":"2007","journal-title":"J. Virol."},{"key":"2025030707295843900_r29","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.4049\/jimmunol.1202861","article-title":"Comparative analysis of the magnitude, quality, phenotype, and protective capacity of simian immunodeficiency virus Gag-specific CD8+ T cells following human-, simian-, and chimpanzee-derived recombinant adenoviral vector immunization","volume":"190","author":"Quinn","year":"2013","journal-title":"J. Immunol."},{"key":"2025030707295843900_r30","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.coi.2011.03.006","article-title":"Viral vectors as vaccine platforms: deployment in sight","volume":"23","author":"Rollier","year":"2011","journal-title":"Curr. Opin. Immunol."},{"key":"2025030707295843900_r31","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tube.2006.01.017","article-title":"Use of recombinant virus-vectored tuberculosis vaccines for respiratory mucosal immunization","volume":"86","author":"Xing","year":"2006","journal-title":"Tuberculosis (Edinb.)"},{"key":"2025030707295843900_r32","doi-asserted-by":"crossref","first-page":"6357","DOI":"10.4049\/jimmunol.173.10.6357","article-title":"Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis","volume":"173","author":"Wang","year":"2004","journal-title":"J. Immunol."},{"key":"2025030707295843900_r33","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.it.2010.05.002","article-title":"Airway luminal T cells: a newcomer on the stage of TB vaccination strategies","volume":"31","author":"Jeyanathan","year":"2010","journal-title":"Trends Immunol."},{"key":"2025030707295843900_r34","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.4049\/jimmunol.178.4.2387","article-title":"Mucosal luminal manipulation of T cell geography switches on protective efficacy by otherwise ineffective parenteral genetic immunization","volume":"178","author":"Santosuosso","year":"2007","journal-title":"J. Immunol."},{"key":"2025030707295843900_r35","doi-asserted-by":"crossref","first-page":"7986","DOI":"10.4049\/jimmunol.174.12.7986","article-title":"Mechanisms of mucosal and parenteral tuberculosis vaccinations: adenoviral-based mucosal immunization preferentially elicits sustained accumulation of immune protective CD4 and CD8 T cells within the airway lumen","volume":"174","author":"Santosuosso","year":"2005","journal-title":"J. Immunol."},{"key":"2025030707295843900_r36","doi-asserted-by":"crossref","first-page":"4955","DOI":"10.4049\/jimmunol.181.7.4955","article-title":"Multifunctional, high-level cytokine-producing Th1 cells in the lung, but not spleen, correlate with protection against Mycobacterium tuberculosis aerosol challenge in mice","volume":"181","author":"Forbes","year":"2008","journal-title":"J. Immunol."},{"key":"2025030707295843900_r37","doi-asserted-by":"crossref","first-page":"4634","DOI":"10.1128\/IAI.00517-06","article-title":"Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis","volume":"74","author":"Santosuosso","year":"2006","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r38","doi-asserted-by":"crossref","first-page":"e5856","DOI":"10.1371\/journal.pone.0005856","article-title":"Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis","volume":"4","author":"Xing","year":"2009","journal-title":"PLoS ONE"},{"key":"2025030707295843900_r39","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1128\/CVI.00690-12","article-title":"Evaluation of the safety and immunogenicity of a candidate tuberculosis vaccine, MVA85A, delivered by aerosol to the lungs of macaques","volume":"20","author":"White","year":"2013","journal-title":"Clin. Vaccine Immunol."},{"key":"2025030707295843900_r40","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":"Havenga","year":"2006","journal-title":"J. Gen. Virol."},{"key":"2025030707295843900_r41","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1600-0684.2012.00536.x","article-title":"The non-human primate model of tuberculosis","volume":"41","author":"Kaushal","year":"2012","journal-title":"J. Med. Primatol."},{"key":"2025030707295843900_r42","doi-asserted-by":"crossref","first-page":"S210","DOI":"10.1086\/313885","article-title":"A nonhuman primate model for preclinical testing of new tuberculosis vaccines","volume":"30","author":"McMurray","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"2025030707295843900_r43","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 \u03b3 interferon","volume":"75","author":"Radosevic","year":"2007","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r44","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1164\/rccm.200910-1484OC","article-title":"The novel tuberculosis vaccine, AERAS-402, induces robust and polyfunctional CD4+ and CD8+ T cells in adults","volume":"181","author":"Abel","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025030707295843900_r45","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1016\/j.vaccine.2012.01.048","article-title":"A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity","volume":"30","author":"Hoft","year":"2012","journal-title":"Vaccine"},{"key":"2025030707295843900_r46","doi-asserted-by":"crossref","first-page":"e3790","DOI":"10.1371\/journal.pone.0003790","article-title":"rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector","volume":"3","author":"Magalhaes","year":"2008","journal-title":"PLoS ONE"},{"key":"2025030707295843900_r47","doi-asserted-by":"crossref","first-page":"L731","DOI":"10.1152\/ajplung.00120.2011","article-title":"Stereological analysis of bacterial load and lung lesions in nonhuman primates (rhesus macaques) experimentally infected with Mycobacterium tuberculosis","volume":"301","author":"Luciw","year":"2011","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"2025030707295843900_r48","doi-asserted-by":"crossref","first-page":"11007","DOI":"10.1128\/JVI.05346-11","article-title":"Durable mucosal simian immunodeficiency virus-specific effector memory T lymphocyte responses elicited by recombinant adenovirus vectors in rhesus monkeys","volume":"85","author":"Li","year":"2011","journal-title":"J. Virol."},{"key":"2025030707295843900_r49","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/cyto.a.21015","article-title":"SPICE: exploration and analysis of post-cytometric complex multivariate datasets","volume":"79","author":"Roederer","year":"2011","journal-title":"Cytometry A"},{"key":"2025030707295843900_r50","doi-asserted-by":"crossref","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":"2025030707295843900_r51","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/1074-7613(95)90001-2","article-title":"Tumor necrosis factor-\u03b1 is required in the protective immune response against Mycobacterium tuberculosis in mice","volume":"2","author":"Flynn","year":"1995","journal-title":"Immunity"},{"key":"2025030707295843900_r52","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":"Cooper","year":"1993","journal-title":"J. Exp. Med."},{"key":"2025030707295843900_r53","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1002\/pmic.201100544","article-title":"Deciphering the proteome of the in vivo diagnostic reagent \u201cpurified protein derivative\u201d from Mycobacterium tuberculosis","volume":"12","author":"Cho","year":"2012","journal-title":"Proteomics"},{"key":"2025030707295843900_r54","doi-asserted-by":"publisher","DOI":"10.4161\/hv.29108","article-title":"A nonhuman primate toxicology and immunogenicity study evaluating aerosol delivery of AERAS-402\/Ad35 vaccine: evidence for transient t cell responses in peripheral blood and robust sustained responses in the lungs","author":"Hokey","year":"2014","journal-title":"Hum. Vaccin. Immunother."},{"key":"2025030707295843900_r55","doi-asserted-by":"crossref","first-page":"e5930","DOI":"10.1371\/journal.pone.0005930","article-title":"Protection and polyfunctional T cells induced by Ag85B-TB10.4\/IC31 against Mycobacterium tuberculosis is highly dependent on the antigen dose","volume":"4","author":"Aagaard","year":"2009","journal-title":"PLoS ONE"},{"key":"2025030707295843900_r56","doi-asserted-by":"crossref","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":"2025030707295843900_r57","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":"Seder","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025030707295843900_r58","doi-asserted-by":"crossref","first-page":"9590","DOI":"10.1128\/JVI.00740-12","article-title":"Vaccination with adenovirus serotypes 35, 26, and 48 elicits higher levels of innate cytokine responses than adenovirus serotype 5 in rhesus monkeys","volume":"86","author":"Teigler","year":"2012","journal-title":"J. Virol."},{"key":"2025030707295843900_r59","doi-asserted-by":"crossref","first-page":"6109","DOI":"10.4049\/jimmunol.1103717","article-title":"Type I IFN induced by adenovirus serotypes 28 and 35 has multiple effects on T cell immunogenicity","volume":"188","author":"Johnson","year":"2012","journal-title":"J. Immunol."},{"key":"2025030707295843900_r60","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.4049\/jimmunol.179.3.1721","article-title":"Myeloid and plasmacytoid dendritic cells are susceptible to recombinant adenovirus vectors and stimulate polyfunctional memory T cell responses","volume":"179","author":"Lore","year":"2007","journal-title":"J. Immunol."},{"key":"2025030707295843900_r61","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1084\/jem.20052433","article-title":"Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates","volume":"203","author":"Wille-Reece","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025030707295843900_r62","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.4049\/jimmunol.158.4.1949","article-title":"Human T cell responses induced by vaccination with Mycobacterium bovis bacillus Calmette-Gu\u00e9rin","volume":"158","author":"Ravn","year":"1997","journal-title":"J. Immunol."},{"key":"2025030707295843900_r63","doi-asserted-by":"crossref","first-page":"e6559","DOI":"10.1371\/journal.pone.0006559","article-title":"Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies","volume":"4","author":"Jiang","year":"2009","journal-title":"PLoS ONE"},{"key":"2025030707295843900_r64","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/S1473-3099(11)70240-7","article-title":"DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials","volume":"11","author":"Ledgerwood","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"2025030707295843900_r65","doi-asserted-by":"crossref","first-page":"5179","DOI":"10.1016\/j.vaccine.2010.05.075","article-title":"Nasal associated lymphoid tissue (NALT) contributes little to protection against aerosol challenge with Mycobacterium tuberculosis after immunisation with a recombinant adenoviral vaccine","volume":"28","author":"Ronan","year":"2010","journal-title":"Vaccine"},{"key":"2025030707295843900_r66","doi-asserted-by":"crossref","first-page":"e5264","DOI":"10.1371\/journal.pone.0005264","article-title":"MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques","volume":"4","author":"Verreck","year":"2009","journal-title":"PLoS ONE"},{"key":"2025030707295843900_r67","doi-asserted-by":"crossref","first-page":"e27477","DOI":"10.1371\/journal.pone.0027477","article-title":"Simultaneous immunization against tuberculosis","volume":"6","author":"Tchilian","year":"2011","journal-title":"PLoS ONE"},{"key":"2025030707295843900_r68","doi-asserted-by":"crossref","first-page":"205ra134","DOI":"10.1126\/scitranslmed.3006843","article-title":"A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-adenovirus immunity","volume":"5","author":"Smaill","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"2025030707295843900_r69","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1128\/iai.64.8.3038-3047.1996","article-title":"Novel insights into the genetics, biochemistry, and immunocytochemistry of the 30-kilodalton major extracellular protein of Mycobacterium tuberculosis","volume":"64","author":"Harth","year":"1996","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r70","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1128\/mr.56.4.648-661.1992","article-title":"The antigen 85 complex: a major secretion product of Mycobacterium tuberculosis","volume":"56","author":"Wiker","year":"1992","journal-title":"Microbiol. Rev."},{"key":"2025030707295843900_r71","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.1128\/IAI.70.10.5446-5453.2002","article-title":"Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family","volume":"70","author":"Skj\u00f8t","year":"2002","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r72","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1586\/erv.11.28","article-title":"Tuberculosis vaccines in clinical trials","volume":"10","author":"Rowland","year":"2011","journal-title":"Expert Rev. Vaccines"},{"key":"2025030707295843900_r73","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/nm1128","article-title":"Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans","volume":"10","author":"McShane","year":"2004","journal-title":"Nat. Med."},{"key":"2025030707295843900_r74","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1016\/j.vaccine.2012.12.042","article-title":"Comparing the safety and immunogenicity of a candidate TB vaccine MVA85A administered by intramuscular and intradermal delivery","volume":"31","author":"Meyer","year":"2013","journal-title":"Vaccine"},{"key":"2025030707295843900_r75","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/eji.200939754","article-title":"Modified vaccinia Ankara-expressing Ag85A, a novel tuberculosis vaccine, is safe in adolescents and children, and induces polyfunctional CD4+ T cells","volume":"40","author":"Scriba","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"2025030707295843900_r76","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1093\/infdis\/jir195","article-title":"Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants","volume":"203","author":"Scriba","year":"2011","journal-title":"J. Infect. Dis."},{"key":"2025030707295843900_r77","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":"Aagaard","year":"2011","journal-title":"Nat. Med."},{"key":"2025030707295843900_r78","doi-asserted-by":"crossref","first-page":"5452","DOI":"10.1016\/j.vaccine.2006.03.072","article-title":"Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31","volume":"24","author":"Agger","year":"2006","journal-title":"Vaccine"},{"key":"2025030707295843900_r79","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1128\/iai.62.6.2536-2544.1994","article-title":"Effective vaccination of mice against Mycobacterium tuberculosis infection with a soluble mixture of secreted mycobacterial proteins","volume":"62","author":"Andersen","year":"1994","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r80","doi-asserted-by":"crossref","first-page":"e5139","DOI":"10.1371\/journal.pone.0005139","article-title":"CD4 and CD8 T cell responses to the M. tuberculosis Ag85B-TB10.4 promoted by adjuvanted subunit, adenovector or heterologous prime boost vaccination","volume":"4","author":"Elvang","year":"2009","journal-title":"PLoS ONE"},{"key":"2025030707295843900_r81","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.1128\/IAI.72.10.6148-6150.2004","article-title":"Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT-6 in the aerosol guinea pig model","volume":"72","author":"Olsen","year":"2004","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r82","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1016\/j.vaccine.2010.02.094","article-title":"Ag85B-ESAT-6 adjuvanted with IC31 promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in naive human volunteers","volume":"28","author":"van Dissel","year":"2010","journal-title":"Vaccine"},{"key":"2025030707295843900_r83","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1086\/592450","article-title":"A new recombinant bacille Calmette-Gu\u00e9rin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers","volume":"198","author":"Hoft","year":"2008","journal-title":"J. Infect. Dis."},{"key":"2025030707295843900_r84","doi-asserted-by":"crossref","first-page":"13853","DOI":"10.1073\/pnas.250480397","article-title":"Recombinant bacillus Calmette-Gu\u00e9rin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model","volume":"97","author":"Horwitz","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707295843900_r85","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1016\/j.vaccine.2009.05.048","article-title":"Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis","volume":"27","author":"Sun","year":"2009","journal-title":"Vaccine"},{"key":"2025030707295843900_r86","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1128\/IAI.73.6.3814-3816.2005","article-title":"Boosting with poxviruses enhances Mycobacterium bovis BCG efficacy against tuberculosis in guinea pigs","volume":"73","author":"Williams","year":"2005","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r87","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1128\/CVI.00079-10","article-title":"Establishment of an aerosol challenge model of tuberculosis in rhesus macaques and an evaluation of endpoints for vaccine testing","volume":"17","author":"Sharpe","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"2025030707295843900_r88","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":"Tameris","year":"2013","journal-title":"Lancet"},{"key":"2025030707295843900_r89","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":"Bold","year":"2011","journal-title":"PLoS Pathog."},{"key":"2025030707295843900_r90","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1172\/JCI46252","article-title":"The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection","volume":"122","author":"Lin","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2025030707295843900_r91","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1128\/IAI.72.4.2420-2424.2004","article-title":"Effect of growth state on transcription levels of genes encoding major secreted antigens of Mycobacterium tuberculosis in the mouse lung","volume":"72","author":"Shi","year":"2004","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r92","doi-asserted-by":"crossref","first-page":"115ra112","DOI":"10.1126\/scitranslmed.3002925","article-title":"Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species","volume":"4","author":"Colloca","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"2025030707295843900_r93","doi-asserted-by":"crossref","first-page":"11497","DOI":"10.1073\/pnas.201404898","article-title":"Divergent effect of bacillus Calmette-Gu\u00e9rin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: implications for primate models in tuberculosis vaccine research","volume":"98","author":"Langermans","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030707295843900_r94","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.tube.2009.09.002","article-title":"Determination of lesion volume by MRI and stereology in a macaque model of tuberculosis","volume":"89","author":"Sharpe","year":"2009","journal-title":"Tuberculosis (Edinb.)"},{"key":"2025030707295843900_r95","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1749-6632.1968.tb16710.x","article-title":"Biology of the mycobacterioses. Simian tuberculosis: immunologic aspects","volume":"154","author":"Good","year":"1968","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2025030707295843900_r96","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.jcpa.2013.05.005","article-title":"Early lesions following aerosol infection of rhesus macaques (Macaca mulatta) with Mycobacterium tuberculosis strain H37RV","volume":"149","author":"Rayner","year":"2013","journal-title":"J. Comp. Pathol."},{"key":"2025030707295843900_r97","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/j.1600-0684.2004.00062.x","article-title":"Evidence for a rhesus monkey model of asymptomatic tuberculosis","volume":"33","author":"Gormus","year":"2004","journal-title":"J. Med. Primatol."},{"key":"2025030707295843900_r98","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.1128\/IAI.71.10.5831-5844.2003","article-title":"Experimental Mycobacterium tuberculosis infection of cynomolgus macaques closely resembles the various manifestations of human M. tuberculosis infection","volume":"71","author":"Capuano","year":"2003","journal-title":"Infect. Immun."},{"key":"2025030707295843900_r99","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nm0496-430","article-title":"The Philippine cynomolgus monkey (Macaca fasicularis) provides a new nonhuman primate model of tuberculosis that resembles human disease","volume":"2","author":"Walsh","year":"1996","journal-title":"Nat. Med."},{"key":"2025030707295843900_r100","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nm.3412","article-title":"Sterilization of granulomas is common in active and latent tuberculosis despite within-host variability in bacterial killing","volume":"20","author":"Lin","year":"2014","journal-title":"Nat. Med."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/193\/4\/1799\/61494923\/1400676.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/193\/4\/1799\/61494923\/1400676.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:56:25Z","timestamp":1741334185000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/193\/4\/1799\/7960418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":100,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,8,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1400676","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,8]]},"published":{"date-parts":[[2014,8]]}}}