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Simple measurement of interferon\u2010<jats:italic>\u03b3<\/jats:italic> frequency or production per se does not provide adequate prediction of immune protection. In this study, we examined the relationship between T\u2010cell immune responses and protective efficacy conferred by the heterologous vaccination strategy, bacillus Calmette\u2013Gu\u00e9rin (<jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content>) prime\u2010Ag85A <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> boost (B\/D), in an early challenge mouse model of pulmonary tuberculosis. The results demonstrated that mice vaccinated with the B\/D regimen had a significantly reduced bacillary load compared with <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content>\u2010vaccinated mice, and the reduction in colony\u2010forming units was associated with decreased pathology and lower levels of inflammatory cytokines in the infected lungs. Further analysis of immunogenicity showed that the superior protection afforded by the B\/D regimen was associated with significantly increased frequency of splenic interleukin\u20102 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102) \u2010producing <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 T cells and increased <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102 production when measured as integrated mean fluorescence intensity post\u2010vaccination as well. These data suggest that measurement of elevated frequency of <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102\u2010producing <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4 T cells or <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20102 production in the spleens of vaccinated mice can predict vaccine efficacy, at least in the B\/D strategy, and add to the accumulating body of evidence suggesting that <jats:styled-content style=\"fixed-case\">BCG<\/jats:styled-content> prime\u2010boost strategies may be a useful approach to the control of <jats:italic><jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>.\u00a0tuberclosis<\/jats:italic> infection.<\/jats:p>","DOI":"10.1111\/imm.12348","type":"journal-article","created":{"date-parts":[[2014,6,25]],"date-time":"2014-06-25T14:03:12Z","timestamp":1403704992000},"page":"661-669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Enhanced protective efficacy against <i><scp>M<\/scp>ycobacterium tuberculosis<\/i> afforded by <scp>BCG<\/scp> prime\u2010<scp>DNA<\/scp> boost regimen in an early challenge mouse model is associated with increased splenic interleukin\u20102\u2010producing <scp>CD<\/scp>4 T\u2010cell frequency post\u2010vaccination"],"prefix":"10.1111","volume":"143","author":[{"given":"Han","family":"Kang","sequence":"first","affiliation":[{"name":"Shanghai Public Health Clinical Centre Fudan University Shanghai China"},{"name":"Key Laboratory of Medical Molecular Virology of MOE\/MOH Shanghai Medical College Fudan University Shanghai 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