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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-10-21
pubmed:abstractText
T-cell mediated immune responses are key determinants to the natural course of infection caused by intracellular parasites such as Leishmania. Thus, T-cell activating proteins of these microbes continue to generate active interest particularly in view of their possible role in the design and development of newer and more effective vaccines. We have recently reported the presence of T-cell immunostimulatory antigens with the high-molecular-weight (MW) fractions (134-64.2 kDa) of whole Leishmania donovani antigen (strain 2001), which stimulated variable amounts of IFN-gamma, IL-12 and IL-10 in exposed immune individuals. The present study was undertaken to further evaluate these high-MW antigenic fractions (MW range >100-60 kDa) for potential protective efficacy. The high-MW region of the parasite was resolved into five antigenic fractions (Prep A-E) using continuous elution gel electrophoresis. Prior to in vivo protection studies in hamsters, these fractions were used to evaluate in vitro cellular responses in eight Leishmania-exposed individuals and treated cured hamsters. The protective efficacy of prep (A + B), C, D and E in combination with BCG was evaluated in inbred hamsters using standard immunization protocol. Proliferative responses were seen in all eight of eight exposed individuals to prep D [median stimulation index (SI): 5.2 (range 3.9-7.1)] and E [median SI: 5.6 (range 4.4-8.2)], five of eight individuals to prep B and prep C and three of eight to prep A [median SI: 0.2 (range 0.1-7.2)]. The median proliferative responses to prep D and prep E were significantly higher than to fraction prep A; (P < 0.05) but not to prep B and prep C. However, prep A-E induced equivalent levels of IFN-gamma, IL-10 and IL-12 cytokines. Fractions D and E also exhibited marked parasite inhibition in spleen (52.5% and 73.7%) and liver (65% and 80.2%) as compared with prep (A + B) (23% in spleen and 24% in liver) and prep C (38% in spleen and 24% in liver). Prep D and prep E vaccinated animals showed higher in vitro stimulatory responses (mean SI: 6.6 and 8.8) and nitric oxide (NO) induction (mean NO levels: 6.4 and 10.7 mug/ml) against whole cell extract as compared with other groups. The protection also correlated with presence of suppressed Leishmania-specific IgG levels in prep D and prep E immunized hamsters. These studies indicate the presence of immunostimulatory and protective molecules in 60-80 kDa region of L. donovani, which may be further exploited for developing a subunit vaccine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1365-3083
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
68
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
492-501
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:18803606-Adult, pubmed-meshheading:18803606-Animals, pubmed-meshheading:18803606-Antibodies, Protozoan, pubmed-meshheading:18803606-Antigens, Protozoan, pubmed-meshheading:18803606-Cell Proliferation, pubmed-meshheading:18803606-Cricetinae, pubmed-meshheading:18803606-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:18803606-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:18803606-Female, pubmed-meshheading:18803606-Humans, pubmed-meshheading:18803606-Immunization, pubmed-meshheading:18803606-Interferon-gamma, pubmed-meshheading:18803606-Interleukin-10, pubmed-meshheading:18803606-Interleukin-12, pubmed-meshheading:18803606-Leishmania donovani, pubmed-meshheading:18803606-Leishmaniasis, Visceral, pubmed-meshheading:18803606-Liver, pubmed-meshheading:18803606-Lymphocyte Activation, pubmed-meshheading:18803606-Male, pubmed-meshheading:18803606-Mesocricetus, pubmed-meshheading:18803606-Spleen, pubmed-meshheading:18803606-T-Lymphocytes
pubmed:year
2008
pubmed:articleTitle
Prophylactic efficacy of high-molecular-weight antigenic fractions of a recent clinical isolate of Leishmania donovani against visceral leishmaniasis.
pubmed:affiliation
Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't