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There are still no vaccines available for humans and there are limitations associated with the current therapeutic regimens for leishmaniasis. Recently, we reported functional importance of Arabino-1, 4-lactone oxidase (ALO) enzyme from<jats:italic>L. donovani<\/jats:italic>involved in ascorbate biosynthesis pathway. In this study, we have shown that<jats:italic>\u0394ALO<\/jats:italic>parasites do not affect the ability of null mutants to invade visceral organs but severely impair parasite persistence beyond 16 week in BALB\/c mice and hence are safe as an immunogen. Both short term (5 week) and long term (20 week) immunization with<jats:italic>\u0394ALO<\/jats:italic>parasites conferred sustained protection against virulent challenge in BALB\/c mice, activated splenocytes and resulted in induction of pro-inflammatory cytokine response. Protection in immunized mice after challenge correlated with the stimulation of IFN-\u03b3 producing CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells. Antigen-mediated cell immunity correlated with robust nitrite and superoxide generation, macrophage-derived oxidants critical in controlling<jats:italic>Leishmania<\/jats:italic>infection. Our data shows that live attenuated<jats:italic>\u0394ALO<\/jats:italic>parasites are safe, induce protective immunity and can provide sustained protection against<jats:italic>Leishmania donovani.<\/jats:italic>We further conclude that the parasites attenuated in their anti-oxidative defence mechanism can be exploited as vaccine candidates.<\/jats:p>","DOI":"10.1038\/srep10706","type":"journal-article","created":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T15:26:23Z","timestamp":1433258783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Genetically Engineered Ascorbic acid-deficient Live Mutants of Leishmania donovani induce long lasting Protective Immunity against Visceral Leishmaniasis"],"prefix":"10.1038","volume":"5","author":[{"given":"Sneha","family":"Anand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rentala","family":"Madhubala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,6,2]]},"reference":[{"key":"BFsrep10706_CR1","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1006\/cyto.2000.0694","volume":"12","author":"O Bacellar","year":"2000","unstructured":"Bacellar, O., D\u2019Oliveira, A., Jr., Jeronimo, S. & Carvalho, E. 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