Towards an immunosense vaccine to prevent toxoplasmosis: protective Toxoplasma gondii epitopes restricted by HLA-A*0201

Vaccine. 2011 Jan 17;29(4):754-62. doi: 10.1016/j.vaccine.2010.11.015. Epub 2010 Nov 21.

Abstract

The ideal vaccine to protect against toxoplasmosis in humans would include antigens that elicit a protective T helper cell type 1 immune response, and generate long-lived IFN-γ-producing CD8(+) T cells. Herein, we utilized a predictive algorithm to identify candidate HLA-A02 supertype epitopes from Toxoplasma gondii proteins. Thirteen peptides elicited production of IFN-γ from PBMC of HLA-A02 supertype persons seropositive for T. gondii infection but not from seronegative controls. These peptides displayed high-affinity binding to HLA-A02 proteins. Immunization of HLA-A*0201 transgenic mice with these pooled peptides, with a universal CD4(+) epitope peptide called PADRE, formulated with adjuvant GLA-SE, induced CD8(+) T cell IFN-γ production and protected against parasite challenge. Peptides identified in this study provide candidates for inclusion in immunosense epitope-based vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • HLA-A Antigens / immunology*
  • HLA-A2 Antigen
  • Humans
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Transgenic
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Vaccines / genetics
  • Protozoan Vaccines / immunology*
  • Toxoplasma / genetics
  • Toxoplasma / immunology*
  • Toxoplasmosis / immunology
  • Toxoplasmosis / prevention & control*
  • Vaccination / methods

Substances

  • Adjuvants, Immunologic
  • Antigens, Protozoan
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Protozoan Proteins
  • Protozoan Vaccines
  • Interferon-gamma