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Previously, we showed that centrin1 and p27gene deleted live attenuated <jats:italic>Leishmania<\/jats:italic> parasites (<jats:italic>Ld<\/jats:italic>Cen1<jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Ld<\/jats:italic>p27<jats:sup>\u2212\/\u2212<\/jats:sup>) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by <jats:italic>Ld<\/jats:italic>Cen1<jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Ld<\/jats:italic>p27<jats:sup>\u2212\/\u2212<\/jats:sup> in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, <jats:italic>Ld<\/jats:italic>Cen1<jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Ld<\/jats:italic>p27<jats:sup>\u2212\/\u2212<\/jats:sup> strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-\u03b3, TNF-\u03b1, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to <jats:italic>Leishmania<\/jats:italic> (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-\u03b3 secreting CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells and IL-17 secreting CD4<jats:sup>+<\/jats:sup> cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, <jats:italic>Ld<\/jats:italic>Cen1<jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Ld<\/jats:italic>p27<jats:sup>\u2212\/\u2212<\/jats:sup> are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure.<\/jats:p>","DOI":"10.1038\/srep33059","type":"journal-article","created":{"date-parts":[[2016,9,14]],"date-time":"2016-09-14T08:30:19Z","timestamp":1473841819000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs"],"prefix":"10.1038","volume":"6","author":[{"given":"Kumar","family":"Avishek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himanshu","family":"Kaushal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sreenivas","family":"Gannavaram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranadhir","family":"Dey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angamuthu","family":"Selvapandiyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Ramesh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narender Singh","family":"Negi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma S.","family":"Dubey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hira L.","family":"Nakhasi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poonam","family":"Salotra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,9,14]]},"reference":[{"key":"BFsrep33059_CR1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1111\/pim.12007","volume":"34","author":"S Nyl\u00e9n","year":"2012","unstructured":"Nyl\u00e9n, S. & Eidsmo, L. 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