{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T04:23:15Z","timestamp":1769660595137,"version":"3.49.0"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Resistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in \u223c15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB\/c mice demonstrated that the vaccine induced enhanced IFN-\u03b3-producing CD4+ and CD8+ T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-\u03b3 and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-\u03b3 and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.<\/jats:p>","DOI":"10.4049\/jimmunol.0900132","type":"journal-article","created":{"date-parts":[[2009,11,23]],"date-time":"2009-11-23T22:59:20Z","timestamp":1259017160000},"page":"7719-7731","source":"Crossref","is-referenced-by-count":31,"title":["Ubiquitin Conjugation of Open Reading Frame F DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains of\n                    <i>Leishmania donovani<\/i>"],"prefix":"10.1093","volume":"183","author":[{"given":"Ankur","family":"Sharma","sequence":"first","affiliation":[{"name":"School of Life Sciences, Jawaharlal Nehru University , New Delhi,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rentala","family":"Madhubala","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Jawaharlal Nehru University , New Delhi,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,15]]},"reference":[{"key":"2026012811245288300_R1","first-page":"1561","article-title":"Advances in leishmaniasis.","volume-title":"Lancet","year":"2005"},{"key":"2026012811245288300_R2","first-page":"2","article-title":"Trop. 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