{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T10:21:55Z","timestamp":1793701315705,"version":"4.5.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T00:00:00Z","timestamp":1478044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T00:00:00Z","timestamp":1478044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The development of a vaccine for <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (Mtb) has been impeded by the absence of correlates of protective immunity. One correlate would be the ability of cells induced by vaccination to recognize the Mtb-infected cell. AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA expressing a fusion protein of Mtb antigens 85A, 85B and TB10.4. We undertook a phase I double-blind, randomized placebo controlled trial of vaccination with AERAS-402 following BCG. Analysis of the vaccine-induced immune response revealed strong antigen-specific polyfunctional CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cell responses. However, analysis of the vaccine-induced CD8<jats:sup>+<\/jats:sup> T cells revealed that in many instances these cells did not recognize the Mtb-infected cell. Our findings highlight the measurement of vaccine-induced, polyfunctional T cells may not reflect the extent or degree to which these cells are capable of identifying the Mtb-infected cell and correspondingly, the value of detailed experimental medicine studies early in vaccine development.<\/jats:p>","DOI":"10.1038\/srep36355","type":"journal-article","created":{"date-parts":[[2016,11,2]],"date-time":"2016-11-02T11:12:16Z","timestamp":1478085136000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine"],"prefix":"10.1038","volume":"6","author":[{"given":"Melissa","family":"Nyendak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn M.","family":"Swarbrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Cansler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ervina Winata","family":"Huff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hokey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewellys","family":"Barker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretta","family":"Blatner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerald","family":"Sadoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macaya","family":"Douoguih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Pau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Lewinsohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Lewinsohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,2]]},"reference":[{"key":"BFsrep36355_CR1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1146\/annurev-publhealth-031912-114431","volume":"34","author":"C Dye","year":"2013","unstructured":"Dye, C., Glaziou, P., Floyd, K. & Raviglione, M. Prospects for tuberculosis elimination. Annu Rev Public Health 34, 271\u2013286, doi: 10.1146\/annurev-publhealth-031912-114431 (2013).","journal-title":"Annu Rev Public Health"},{"key":"BFsrep36355_CR2","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nri3259","volume":"12","author":"JD Ernst","year":"2012","unstructured":"Ernst, J. D. The immunological life cycle of tuberculosis. Nat Rev Immunol 12, 581\u2013591, doi: 10.1038\/nri3259 (2012).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep36355_CR3","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nrmicro3230","volume":"12","author":"C Nunes-Alves","year":"2014","unstructured":"Nunes-Alves, C. et al. In search of a new paradigm for protective immunity to TB. Nat Rev Microbiol 12, 289\u2013299, doi: 10.1038\/nrmicro3230 (2014).","journal-title":"Nat Rev Microbiol"},{"key":"BFsrep36355_CR4","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1146\/annurev.immunol.021908.132703","volume":"27","author":"AM Cooper","year":"2009","unstructured":"Cooper, A. M. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27, 393\u2013422, doi: 10.1146\/annurev.immunol.021908.132703 (2009).","journal-title":"Annu Rev Immunol"},{"key":"BFsrep36355_CR5","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1146\/annurev-immunol-032712-095939","volume":"31","author":"A O\u2019Garra","year":"2013","unstructured":"O\u2019Garra, A. et al. The immune response in tuberculosis. Annu Rev Immunol 31, 475\u2013527, doi: 10.1146\/annurev-immunol-032712-095939 (2013).","journal-title":"Annu Rev Immunol"},{"key":"BFsrep36355_CR6","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.4161\/hv.25427","volume":"9","author":"DA Hokey","year":"2013","unstructured":"Hokey, D. A. & Ginsberg, A. The current state of tuberculosis vaccines. Hum Vaccin Immunother 9, 2142\u20132146, doi: 10.4161\/hv.25427 (2013).","journal-title":"Hum Vaccin Immunother"},{"key":"BFsrep36355_CR7","doi-asserted-by":"publisher","first-page":"8047","DOI":"10.4049\/jimmunol.0801592","volume":"182","author":"T Lindenstrom","year":"2009","unstructured":"Lindenstrom, T. et al. Tuberculosis subunit vaccination provides long-term protective immunity characterized by multifunctional CD4 memory T cells. J Immunol 182, 8047\u20138055, doi: 10.4049\/jimmunol.0801592 (2009).","journal-title":"J Immunol"},{"key":"BFsrep36355_CR8","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1002\/eji.200737504","volume":"37","author":"NE Beveridge","year":"2007","unstructured":"Beveridge, N. E. et al. Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis-specific CD4+ memory T lymphocyte populations. Eur J Immunol 37, 3089\u20133100, doi: 10.1002\/eji.200737504 (2007).","journal-title":"Eur J Immunol"},{"key":"BFsrep36355_CR9","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1002\/eji.201040731","volume":"40","author":"KA Wilkinson","year":"2010","unstructured":"Wilkinson, K. A. & Wilkinson, R. J. Polyfunctional T cells in human tuberculosis. Eur J Immunol 40, 2139\u20132142, doi: 10.1002\/eji.201040731 (2010).","journal-title":"Eur J Immunol"},{"key":"BFsrep36355_CR10","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nri2274","volume":"8","author":"RA Seder","year":"2008","unstructured":"Seder, R. A., Darrah, P. A. & Roederer, M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8, 247\u2013258, doi: 10.1038\/nri2274 (2008).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep36355_CR11","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/S0140-6736(13)60177-4","volume":"381","author":"MD Tameris","year":"2013","unstructured":"Tameris, M. D. et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet 381, 1021\u20131028, doi: 10.1016\/S0140-6736(13)60177-4 (2013).","journal-title":"Lancet"},{"key":"BFsrep36355_CR12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1111\/j.1600-065X.2010.00997.x","volume":"240","author":"DA Lewinsohn","year":"2011","unstructured":"Lewinsohn, D. A., Gold, M. C. & Lewinsohn, D. M. Views of immunology: effector T cells. Immunol Rev 240, 25\u201339, doi: 10.1111\/j.1600-065X.2010.00997.x (2011).","journal-title":"Immunol Rev"},{"key":"BFsrep36355_CR13","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.4049\/jimmunol.160.5.2374","volume":"160","author":"DM Lewinsohn","year":"1998","unstructured":"Lewinsohn, D. M. et al. Human purified protein derivative-specific CD4+ T cells use both CD95-dependent and CD95-independent cytolytic mechanisms. J Immunol 160, 2374\u20132379 (1998).","journal-title":"J Immunol"},{"key":"BFsrep36355_CR14","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1164\/rccm.200306-837OC200306-837OC","volume":"168","author":"DA Lewinsohn","year":"2003","unstructured":"Lewinsohn, D. A. et al. Mycobacterium tuberculosis-specific CD8+ T cells preferentially recognize heavily infected cells. Am J Respir Crit Care Med 168, 1346\u20131352, doi: 10.1164\/rccm.200306-837OC200306-837OC [pii] (2003).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep36355_CR15","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1371\/journal.ppat.0030127","volume":"3","author":"DA Lewinsohn","year":"2007","unstructured":"Lewinsohn, D. A. et al. Immunodominant tuberculosis CD8 antigens preferentially restricted by HLA-B. PLoS Pathog 3, 1240\u20131249, doi: 10.1371\/journal.ppat.0030127 (2007).","journal-title":"PLoS Pathog"},{"key":"BFsrep36355_CR16","doi-asserted-by":"publisher","first-page":"12210","DOI":"10.1073\/pnas.210391497","volume":"97","author":"S Cho","year":"2000","unstructured":"Cho, S. et al. Antimicrobial activity of MHC class I-restricted CD8+ T cells in human tuberculosis. Proc Natl Acad Sci USA 97, 12210\u201312215, doi: 10.1073\/pnas.210391497 (2000).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep36355_CR17","doi-asserted-by":"publisher","first-page":"12013","DOI":"10.1073\/pnas.89.24.12013","volume":"89","author":"JL Flynn","year":"1992","unstructured":"Flynn, J. L., Goldstein, M. M., Triebold, K. J., Koller, B. & Bloom, B. R. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc Natl Acad Sci USA 89, 12013\u201312017 (1992).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep36355_CR18","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1073\/pnas.95.1.270","volume":"95","author":"A Lalvani","year":"1998","unstructured":"Lalvani, A. et al. Human cytolytic and interferon gamma-secreting CD8+ T lymphocytes specific for Mycobacterium tuberculosis. Proc Natl Acad Sci USA 95, 270\u2013275 (1998).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep36355_CR19","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1084\/jem.187.10.1633","volume":"187","author":"DM Lewinsohn","year":"1998","unstructured":"Lewinsohn, D. M. et al. Characterization of human CD8+ T cells reactive with Mycobacterium tuberculosis-infected antigen-presenting cells. J Exp Med 187, 1633\u20131640 (1998).","journal-title":"J Exp Med"},{"key":"BFsrep36355_CR20","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00281-015-0490-8","volume":"37","author":"PL Lin","year":"2015","unstructured":"Lin, P. L. & Flynn, J. L. CD8 T cells and Mycobacterium tuberculosis infection. Semin Immunopathol 37, 239\u2013249, doi: 10.1007\/s00281-015-0490-8 (2015).","journal-title":"Semin Immunopathol"},{"key":"BFsrep36355_CR21","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1164\/rccm.200910-1484OC","volume":"181","author":"B Abel","year":"2010","unstructured":"Abel, B. et al. The novel tuberculosis vaccine, AERAS-402, induces robust and polyfunctional CD4+ and CD8+ T cells in adults. Am J Respir Crit Care Med 181, 1407\u20131417, doi: 10.1164\/rccm.200910-1484OC (2010).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep36355_CR22","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1099\/vir.0.81956-0","volume":"87","author":"M Havenga","year":"2006","unstructured":"Havenga, M. et al. Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells. J Gen Virol 87, 2135\u20132143, doi: 10.1099\/vir.0.81956-0 (2006).","journal-title":"J Gen Virol"},{"key":"BFsrep36355_CR23","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1016\/j.vaccine.2012.01.048","volume":"30","author":"DF Hoft","year":"2012","unstructured":"Hoft, D. F. et al. A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity. Vaccine 30, 2098\u20132108, doi: 10.1016\/j.vaccine.2012.01.048 (2012).","journal-title":"Vaccine"},{"key":"BFsrep36355_CR24","doi-asserted-by":"publisher","first-page":"5908","DOI":"10.1016\/j.vaccine.2014.09.001","volume":"32","author":"BM Kagina","year":"2014","unstructured":"Kagina, B. M. et al. The novel tuberculosis vaccine, AERAS-402, is safe in healthy infants previously vaccinated with BCG, and induces dose-dependent CD4 and CD8T cell responses. Vaccine 32, 5908\u20135917, doi: 10.1016\/j.vaccine.2014.09.001 (2014).","journal-title":"Vaccine"},{"key":"BFsrep36355_CR25","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1016\/j.vaccine.2015.02.004","volume":"33","author":"GJ Churchyard","year":"2015","unstructured":"Churchyard, G. J. et al. The safety and immunogenicity of an adenovirus type 35-vectored TB vaccine in HIV-infected, BCG-vaccinated adults with CD4(+) T cell counts &gt;350 cells\/mm(3). Vaccine 33, 1890\u20131896, doi: 10.1016\/j.vaccine.2015.02.004 (2015).","journal-title":"Vaccine"},{"key":"BFsrep36355_CR26","doi-asserted-by":"publisher","first-page":"726","DOI":"10.7326\/0003-4819-152-11-201006010-00232","volume":"152","author":"KF Schulz","year":"2010","unstructured":"Schulz, K. F., Altman, D. G. & Moher, D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med 152, 726\u2013732, doi: 10.7326\/0003-4819-152-11-201006010-00232 (2010).","journal-title":"Ann Intern Med"},{"key":"BFsrep36355_CR27","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1084\/jem.20020609","volume":"196","author":"AS Heinzel","year":"2002","unstructured":"Heinzel, A. S. et al. HLA-E-dependent presentation of Mtb-derived antigen to human CD8+ T cells. J Exp Med 196, 1473\u20131481 (2002).","journal-title":"J Exp Med"},{"key":"BFsrep36355_CR28","doi-asserted-by":"publisher","first-page":"2944","DOI":"10.1016\/j.vaccine.2015.03.070","volume":"33","author":"M Tameris","year":"2015","unstructured":"Tameris, M. et al. A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants. Vaccine 33, 2944\u20132954, doi: 10.1016\/j.vaccine.2015.03.070 (2015).","journal-title":"Vaccine"},{"key":"BFsrep36355_CR29","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1164\/rccm.201003-0334OC","volume":"182","author":"BM Kagina","year":"2010","unstructured":"Kagina, B. M. et al. Specific T cell frequency and cytokine expression profile do not correlate with protection against tuberculosis after bacillus Calmette-Guerin vaccination of newborns. Am J Respir Crit Care Med 182, 1073\u20131079, doi: 10.1164\/rccm.201003-0334OC (2010).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep36355_CR30","doi-asserted-by":"publisher","first-page":"e97515","DOI":"10.1371\/journal.pone.0097515","volume":"9","author":"MJ Harriff","year":"2014","unstructured":"Harriff, M. J. et al. Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8(+) T cells. PLoS One 9, e97515, doi: 10.1371\/journal.pone.0097515 (2014).","journal-title":"PLoS One"},{"key":"BFsrep36355_CR31","doi-asserted-by":"publisher","first-page":"e1000407","DOI":"10.1371\/journal.pbio.1000407","volume":"8","author":"MC Gold","year":"2010","unstructured":"Gold, M. C. et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol 8, e1000407, doi: 10.1371\/journal.pbio.1000407 (2010).","journal-title":"PLoS Biol"},{"key":"BFsrep36355_CR32","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.coi.2012.11.004","volume":"25","author":"M Basler","year":"2013","unstructured":"Basler, M., Kirk, C. J. & Groettrup, M. The immunoproteasome in antigen processing and other immunological functions. Curr Opin Immunol 25, 74\u201380, doi: 10.1016\/j.coi.2012.11.004 (2013).","journal-title":"Curr Opin Immunol"},{"key":"BFsrep36355_CR33","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/S1473-3099(11)70146-3","volume":"11","author":"SH Kaufmann","year":"2011","unstructured":"Kaufmann, S. H. Fact and fiction in tuberculosis vaccine research: 10 years later. Lancet Infect Dis 11, 633\u2013640, doi: 10.1016\/S1473-3099(11)70146-3 (2011).","journal-title":"Lancet Infect Dis"},{"key":"BFsrep36355_CR34","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1086\/344359","volume":"186","author":"DF Hoft","year":"2002","unstructured":"Hoft, D. F. et al. Investigation of the relationships between immune-mediated inhibition of mycobacterial growth and other potential surrogate markers of protective Mycobacterium tuberculosis immunity. J Infect Dis 186, 1448\u20131457, doi: 10.1086\/344359 (2002).","journal-title":"J Infect Dis"},{"key":"BFsrep36355_CR35","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1128\/CVI.00427-13","volume":"20","author":"HA Fletcher","year":"2013","unstructured":"Fletcher, H. A. et al. Inhibition of mycobacterial growth in vitro following primary but not secondary vaccination with Mycobacterium bovis BCG. Clin Vaccine Immunol 20, 1683\u20131689, doi: 10.1128\/CVI.00427-13 (2013).","journal-title":"Clin Vaccine Immunol"},{"key":"BFsrep36355_CR36","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1164\/rccm.201107-1355OC","volume":"185","author":"C Lancioni","year":"2012","unstructured":"Lancioni, C. et al. CD8+ T cells provide an immunologic signature of tuberculosis in young children. Am J Respir Crit Care Med 185, 206\u2013212, doi: 10.1164\/rccm.201107-1355OC (2012).","journal-title":"Am J Respir Crit Care Med"},{"key":"BFsrep36355_CR37","doi-asserted-by":"publisher","first-page":"e67016","DOI":"10.1371\/journal.pone.0067016","volume":"8","author":"DM Lewinsohn","year":"2013","unstructured":"Lewinsohn, D. M. et al. Human CD8 T Cell Antigens\/Epitopes Identified by a Proteomic Peptide Library. PLoS One 8, e67016, doi: 10.1371\/journal.pone.0067016 (2013).","journal-title":"PLoS One"},{"key":"BFsrep36355_CR38","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1002\/eji.201344358","volume":"44","author":"T Lindenstrom","year":"2014","unstructured":"Lindenstrom, T., Aagaard, C., Christensen, D., Agger, E. M. & Andersen, P. High-frequency vaccine-induced CD8(+) T cells specific for an epitope naturally processed during infection with Mycobacterium tuberculosis do not confer protection. Eur J Immunol 44, 1699\u20131709, doi: 10.1002\/eji.201344358 (2014).","journal-title":"Eur J Immunol"},{"key":"BFsrep36355_CR39","doi-asserted-by":"publisher","first-page":"3346","DOI":"10.1002\/eji.200636128","volume":"36","author":"T Bennekov","year":"2006","unstructured":"Bennekov, T. et al. Alteration of epitope recognition pattern in Ag85B and ESAT-6 has a profound influence on vaccine-induced protection against Mycobacterium tuberculosis. Eur J Immunol 36, 3346\u20133355, doi: 10.1002\/eji.200636128 (2006).","journal-title":"Eur J Immunol"},{"key":"BFsrep36355_CR40","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.4049\/jimmunol.0900947","volume":"183","author":"CS Aagaard","year":"2009","unstructured":"Aagaard, C. S., Hoang, T. T., Vingsbo-Lundberg, C., Dietrich, J. & Andersen, P. Quality and vaccine efficacy of CD4+ T cell responses directed to dominant and subdominant epitopes in ESAT-6 from Mycobacterium tuberculosis. J Immunol 183, 2659\u20132668, doi: 10.4049\/jimmunol.0900947 (2009).","journal-title":"J Immunol"},{"key":"BFsrep36355_CR41","doi-asserted-by":"crossref","unstructured":"Olsen, A. W., Hansen, P. R., Holm, A. & Andersen, P. Efficient protection against Mycobacterium tuberculosis by vaccination with a single subdominant epitope from the ESAT-6 antigen. Eur J Immunol 30, 1724\u20131732, doi: 10.1002\/1521-4141(200006)30:6&lt;1724::AID-IMMU1724&gt;3.0.CO;2-A (2000).","DOI":"10.1002\/1521-4141(200006)30:6<1724::AID-IMMU1724>3.0.CO;2-A"},{"key":"BFsrep36355_CR42","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.4049\/jimmunol.1300283","volume":"192","author":"JS Woodworth","year":"2014","unstructured":"Woodworth, J. S. et al. Protective CD4 T cells targeting cryptic epitopes of Mycobacterium tuberculosis resist infection-driven terminal differentiation. J Immunol 192, 3247\u20133258, doi: 10.4049\/jimmunol.1300283 (2014).","journal-title":"J Immunol"},{"key":"BFsrep36355_CR43","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nri2260","volume":"8","author":"V Venturi","year":"2008","unstructured":"Venturi, V., Price, D. A., Douek, D. C. & Davenport, M. P. The molecular basis for public T-cell responses? Nat Rev Immunol 8, 231\u2013238, doi: 10.1038\/nri2260 (2008).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep36355_CR44","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1084\/jem.180.1.83","volume":"180","author":"N Romani","year":"1994","unstructured":"Romani, N. et al. Proliferating dendritic cell progenitors in human blood. J Exp Med 180, 83\u201393 (1994).","journal-title":"J Exp Med"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep36355.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36355","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36355.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:33:55Z","timestamp":1672882435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep36355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,2]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,21]]}},"alternative-id":["BFsrep36355"],"URL":"https:\/\/doi.org\/10.1038\/srep36355","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,2]]},"assertion":[{"value":"29 April 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Aeras TB Vaccine Foundation has licensed technology (not the subject of this research) from OHSU of which Dr. David Lewinsohn and Dr. Deborah Lewinsohn are inventors. OHSU, Dr. David Lewinsohn, and Dr. Deborah Lewinsohn and Dr. Melissa Nyendak have a financial interest in ViTi, Inc., a company that may have a commercial interest in some research results reported herein. These potential conflicts of interest have been reviewed and managed by OHSU.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36355"}}