Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-12-16
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7719-31
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
pubmed:year
2009
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.
pubmed:affiliation
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't