Source:http://linkedlifedata.com/resource/pubmed/id/19933862
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2009-12-16
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pubmed:abstractText |
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 approximately 15% 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-gamma-producing CD4(+) and CD8(+) T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-gamma 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-gamma 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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimony,
http://linkedlifedata.com/resource/pubmed/chemical/Leishmaniasis Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/ORFF protein, Leishmania,
http://linkedlifedata.com/resource/pubmed/chemical/Protozoan Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, Conjugate,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1550-6606
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7719-31
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pubmed:meshHeading |
pubmed-meshheading:19933862-Animals,
pubmed-meshheading:19933862-Antimony,
pubmed-meshheading:19933862-Cells, Cultured,
pubmed-meshheading:19933862-Drug Resistance,
pubmed-meshheading:19933862-Female,
pubmed-meshheading:19933862-Genetic Predisposition to Disease,
pubmed-meshheading:19933862-Immunity, Cellular,
pubmed-meshheading:19933862-Leishmania donovani,
pubmed-meshheading:19933862-Leishmaniasis, Visceral,
pubmed-meshheading:19933862-Leishmaniasis Vaccines,
pubmed-meshheading:19933862-Mice,
pubmed-meshheading:19933862-Mice, Inbred BALB C,
pubmed-meshheading:19933862-Open Reading Frames,
pubmed-meshheading:19933862-Protozoan Proteins,
pubmed-meshheading:19933862-Th1 Cells,
pubmed-meshheading:19933862-Ubiquitin,
pubmed-meshheading:19933862-Vaccines, Conjugate,
pubmed-meshheading:19933862-Vaccines, DNA
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pubmed:year |
2009
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pubmed:articleTitle |
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 Leishmania donovani.
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pubmed:affiliation |
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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