Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines

Hum Vaccin Immunother. 2012 Dec 1;8(12):1769-74. doi: 10.4161/hv.21881. Epub 2012 Aug 24.

Abstract

Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at-risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.

Keywords: EpiMatrix; T cell epitopes; vaccine; visceral leishmaniasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Computational Biology
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Healthy Volunteers
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Leishmania donovani / genetics
  • Leishmania donovani / immunology*
  • Leishmaniasis Vaccines / administration & dosage
  • Leishmaniasis Vaccines / genetics
  • Leishmaniasis Vaccines / immunology*
  • Male
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / immunology*
  • T-Lymphocytes / immunology
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Young Adult

Substances

  • Epitopes, T-Lymphocyte
  • Leishmaniasis Vaccines
  • Vaccines, Subunit
  • Interleukin-10
  • Interferon-gamma
  • Metalloendopeptidases
  • glycoprotein gp63, Leishmania