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Here we produced a dermotropic live attenuated\n                    <jats:italic>centrin<\/jats:italic>\n                    gene deleted\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    (\n                    <jats:italic>LmCen<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ) vaccine under Good Laboratory Practices and demonstrated that a single intradermal injection confers robust and durable protection against lethal VL transmitted naturally via bites of\n                    <jats:italic>L. donovani<\/jats:italic>\n                    -infected sand flies and prevents mortality. Surprisingly, immunogenicity characteristics of\n                    <jats:italic>LmCen<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    parasites revealed activation of common immune pathways like\n                    <jats:italic>L. major<\/jats:italic>\n                    wild type parasites. Spleen cells from\n                    <jats:italic>LmCen<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    immunized and\n                    <jats:italic>L. donovani<\/jats:italic>\n                    challenged hamsters produced significantly higher Th1-associated cytokines including IFN-\u03b3, TNF-\u03b1, and reduced expression of the anti-inflammatory cytokines like IL-10, IL-21, compared to non-immunized challenged animals. PBMCs, isolated from healthy people from non-endemic region, upon\n                    <jats:italic>LmCen<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    infection also induced more IFN-\u03b3 compared to IL-10, consistent with our immunogenicity data in\n                    <jats:italic>LmCen<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    immunized hamsters. This study demonstrates that the\n                    <jats:italic>LmCen<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    parasites are safe and efficacious against VL and is a strong candidate vaccine to be tested in a human clinical trial.\n                  <\/jats:p>","DOI":"10.1038\/s42003-021-02446-x","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T06:04:43Z","timestamp":1627625083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Preclinical validation of a live attenuated dermotropic Leishmania vaccine against vector transmitted fatal visceral 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