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Understanding how functional avidity is maintained in T cells is imperative for immunotherapy. However, studies systematically characterize T cell with high functional avidity induced <jats:italic>in vivo<\/jats:italic> are still lacking. Previously, we and others found vaccinia vectored vaccine (VACV) induced antigen-specific CD8<jats:sup>+<\/jats:sup> T cells with relatively high functional avidity to those from DNA vaccine. Herein, we used functional, immune phenotyping and transcriptomic studies to define the immune signature of these CD8<jats:sup>+<\/jats:sup> T cells with high functional avidity. Antigen-specific CD8<jats:sup>+<\/jats:sup> T cells induced by VACV executed superior <jats:italic>in vivo<\/jats:italic> killing activity and displayed a distinct transcriptional profile, whereas no significantly differences were found in composition of memory sub-populations and cytokine poly-functionality. Transcriptional analyses revealed unique features of VACV induced CD8<jats:sup>+<\/jats:sup> T cells in several biological processes, including transport, cell cycle, cell communication and metabolic processes. In summary, we characterize CD8<jats:sup>+<\/jats:sup> T cells of high functional avidity induced <jats:italic>in vivo<\/jats:italic> by VACV, which not only improves our understanding of adaptive T cell immunity in VACV vaccination, but also provides clues to modulate functional avidity of CD8<jats:sup>+<\/jats:sup> T cells for T cell based immunotherapy.<\/jats:p>","DOI":"10.1038\/srep41558","type":"journal-article","created":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T12:50:16Z","timestamp":1486126216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Immune Signature of Enhanced Functional Avidity CD8+ T Cells in vivo Induced by Vaccinia Vectored Vaccine"],"prefix":"10.1038","volume":"7","author":[{"given":"Zhidong","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songhua","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqing","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenli","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,3]]},"reference":[{"key":"BFsrep41558_CR1","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nm.f.1774","volume":"14","author":"V Appay","year":"2008","unstructured":"Appay, V., Douek, D. 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