Abstract
The meta 1 gene of Leishmania is conserved across the genus and encodes a protein upregulated in metacyclic promastigotes. Meta 1 constitutive overexpressing mutants show increased virulence to mice. In this paper, both meta 1 recombinant protein and plasmids bearing the meta 1 gene were tested for their antigenicity and potential for inducing protective immunity in mice. Vaccination with the recombinant protein induced a predominant Th2-type of response and did not result in protection upon challenge with live parasites. Surprisingly, the expected reversal to a CD4(+) Th1-type of response upon genetic immunisation by the intramuscular route was not observed. Instead, vaccination with either the meta 1 gene alone or in fusion with the monocyte chemotactic protein (MCP)-3 cDNA induced a Th2-type of response that correlated with lack of protection against infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Protozoan / biosynthesis*
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COS Cells / chemistry
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COS Cells / metabolism
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Cell Line
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Chemokine CCL7
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Chlorocebus aethiops
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Cytokines / biosynthesis
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Female
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Leishmania major / immunology*
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Leishmania mexicana / immunology
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Leishmaniasis, Cutaneous / prevention & control
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Leishmaniasis, Diffuse Cutaneous / prevention & control
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Mice
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Mice, Inbred BALB C
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Monocyte Chemoattractant Proteins / biosynthesis
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Monocyte Chemoattractant Proteins / genetics
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Monocyte Chemoattractant Proteins / immunology
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Monocyte Chemoattractant Proteins / therapeutic use
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Protozoan Proteins / administration & dosage*
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology
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Protozoan Vaccines / administration & dosage*
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Protozoan Vaccines / immunology
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Recombinant Proteins / administration & dosage*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology*
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Solubility
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T-Lymphocyte Subsets / immunology
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / immunology
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Vaccines, DNA / therapeutic use
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / immunology
Substances
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Antibodies, Protozoan
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Ccl7 protein, mouse
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Chemokine CCL7
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Cytokines
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Meta1 protein, Leishmania major
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Monocyte Chemoattractant Proteins
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Protozoan Proteins
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Protozoan Vaccines
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Recombinant Proteins
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Vaccines, DNA
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Vaccines, Synthetic