Evaluation of the murine immune response to Leishmania meta 1 antigen delivered as recombinant protein or DNA vaccine

Vaccine. 2002 Nov 1;20(31-32):3755-63. doi: 10.1016/s0264-410x(02)00354-7.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / biosynthesis*
  • COS Cells / chemistry
  • COS Cells / metabolism
  • Cell Line
  • Chemokine CCL7
  • Chlorocebus aethiops
  • Cytokines / biosynthesis
  • Female
  • Leishmania major / immunology*
  • Leishmania mexicana / immunology
  • Leishmaniasis, Cutaneous / prevention & control
  • Leishmaniasis, Diffuse Cutaneous / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Monocyte Chemoattractant Proteins / biosynthesis
  • Monocyte Chemoattractant Proteins / genetics
  • Monocyte Chemoattractant Proteins / immunology
  • Monocyte Chemoattractant Proteins / therapeutic use
  • Protozoan Proteins / administration & dosage*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Vaccines / administration & dosage*
  • Protozoan Vaccines / immunology
  • Recombinant Proteins / administration & dosage*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology*
  • Solubility
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Protozoan
  • Ccl7 protein, mouse
  • Chemokine CCL7
  • Cytokines
  • Meta1 protein, Leishmania major
  • Monocyte Chemoattractant Proteins
  • Protozoan Proteins
  • Protozoan Vaccines
  • Recombinant Proteins
  • Vaccines, DNA
  • Vaccines, Synthetic