{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:58:31Z","timestamp":1790247511224,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T00:00:00Z","timestamp":1192665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the search for effective vaccines against intracellular pathogens such as HIV, tuberculosis and malaria, recombinant viral vectors are increasingly being used to boost previously primed T cell responses. Published data have shown prime\u2010boost vaccination with BCG\u2010MVA85A (modified vaccinia virus Ankara expressing antigen 85A) to be highly immunogenic in humans as measured by <jats:italic>ex vivo<\/jats:italic> IFN\u2010\u03b3 ELISPOT. Here, we used polychromatic flow cytometry to investigate the phenotypic and functional profile of these vaccine\u2010induced <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (<jats:italic>M.tb<\/jats:italic>) antigen 85A\u2010specific responses in greater detail. Promisingly, antigen 85A\u2010specific CD4<jats:sup>+<\/jats:sup> T cells were found to be highly polyfunctional, producing IFN\u2010\u03b3, TNF\u2010\u03b1, IL\u20102 and MIP\u20101\u03b2. Surface staining showed the responding CD4<jats:sup>+<\/jats:sup> T cells to be relatively immature (CD45RO<jats:sup>+<\/jats:sup> CD27<jats:sup>int<\/jats:sup>CD57<jats:sup>\u2013<\/jats:sup>); this observation was supported by the robust proliferative responses observed following antigenic stimulation. Furthermore, these phenotypic and functional properties were independent of clonotypic composition and epitope specificity, which was maintained through the different phases of the vaccine\u2010induced immune response. Overall, these data strongly support the use of MVA85A in humans as a boosting agent to expand polyfunctional <jats:italic>M.tb<\/jats:italic>\u2010specific CD4<jats:sup>+<\/jats:sup> T cells capable of significant secondary responses.<\/jats:p>","DOI":"10.1002\/eji.200737504","type":"journal-article","created":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T19:18:44Z","timestamp":1192735124000},"page":"3089-3100","source":"Crossref","is-referenced-by-count":191,"title":["Immunisation with BCG and recombinant MVA85A induces long\u2010lasting, polyfunctional <i>Mycobacterium tuberculosis<\/i>\u2010specific CD4<sup>+<\/sup> memory T lymphocyte populations"],"prefix":"10.1002","volume":"37","author":[{"given":"Natalie\u2004E.\u2004R.","family":"Beveridge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u2004A.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph\u2004P.","family":"Casazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansar\u2004A.","family":"Pathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare\u2004R.","family":"Sander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tedi\u2004E.","family":"Asher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u2004R.","family":"Ambrozak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa\u2004L.","family":"Precopio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Scheinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola\u2004C.","family":"Alder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Roederer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard\u2004A.","family":"Koup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u2004C.","family":"Douek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian\u2004V.\u2004S.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"McShane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,10,24]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14333-4"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/154510970300200303"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.19.2537"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68507-3"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92348-9"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.3.3.299"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-5-1159"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10847"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00590-06"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.10.4717-4728.2006"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.10.4705-4716.2006"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430340460745757"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5317.1420"},{"key":"e_1_2_7_14_2","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1128\/iai.56.12.3046-3051.1988","article-title":"Characterization of fibronectin\u2010binding antigens released by Mycobacterium tuberculosis and Mycobacterium bovis BCG.","volume":"56","author":"Abou\u2010Zeid C.","year":"1988","journal-title":"Infect. Immun."},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0896-893"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.62.9.3679-3687.1994"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.04.046"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.7088"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.3.1602"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.6.3814-3816.2005"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1128"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5372"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-006-0025-4"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198903023200901"},{"key":"e_1_2_7_25_2","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.4049\/jimmunol.162.9.5407","article-title":"Mice deficient in CD4 T cells have only transiently diminished levels of IFN\u2010gamma, yet succumb to tuberculosis.","volume":"162","author":"Caruso A. M.","year":"1999","journal-title":"J. Immunol."},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.93"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6436-6443.2002"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(03)00022-4"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.6.2249"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2613.2002.00216.x"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.9.4620"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011110"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.4.2174"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324109"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.8.4204"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.6.2272"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4662"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.9.5604"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/35009119"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1416"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(03)00265-5"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052246"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.1.249"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0402-379"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-2103"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100101.151926"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5553"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636390"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.6.3099"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1977"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-12-4818"},{"key":"e_1_2_7_52_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5954"},{"key":"e_1_2_7_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1592"},{"key":"e_1_2_7_54_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.1.117"},{"key":"e_1_2_7_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199909)189:1<127::AID-PATH398>3.0.CO;2-S"},{"key":"e_1_2_7_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3131876"},{"key":"e_1_2_7_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00093-0"},{"key":"e_1_2_7_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/44385"},{"key":"e_1_2_7_59_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.2.1037"},{"key":"e_1_2_7_60_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5217"},{"key":"e_1_2_7_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1371"},{"key":"e_1_2_7_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1469"},{"key":"e_1_2_7_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2006.04.007"},{"key":"e_1_2_7_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90236-4"},{"key":"e_1_2_7_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-305X(02)00039-3"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Feji.200737504","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.200737504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:30:20Z","timestamp":1697081420000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.200737504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10,24]]},"references-count":65,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2007,11]]}},"alternative-id":["10.1002\/eji.200737504"],"URL":"https:\/\/doi.org\/10.1002\/eji.200737504","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10,24]]}}}