Identification of T. gondii epitopes, adjuvants, and host genetic factors that influence protection of mice and humans

Vaccine. 2010 May 21;28(23):3977-89. doi: 10.1016/j.vaccine.2010.03.028. Epub 2010 Mar 26.

Abstract

Toxoplasma gondii is an intracellular parasite that causes severe neurologic and ocular disease in immune-compromised and congenitally infected individuals. There is no vaccine protective against human toxoplasmosis. Herein, immunization of L(d) mice with HF10 (HPGSVNEFDF) with palmitic acid moieties or a monophosphoryl lipid A derivative elicited potent IFN-gamma production from L(d)-restricted CD8(+) T cells in vitro and protected mice. CD8(+) T cell peptide epitopes from T. gondii dense granule proteins GRA 3, 6, 7, and Sag 1, immunogenic in humans for HLA-A02(+), HLA-A03(+), and HLA-B07(+) cells were identified. Since peptide repertoire presented by MHC class I molecules to CD8(+) T cells is shaped by endoplasmic reticulum-associated aminopeptidase (ERAAP), polymorphisms in the human ERAAP gene ERAP1 were studied and associate with susceptibility to human congenital toxoplasmosis (p<0.05). These results have important implications for vaccine development.

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 / pharmacology*
  • Aminopeptidases / genetics
  • Animals
  • Antigens, Protozoan / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Genetic Predisposition to Disease
  • HLA-A Antigens / immunology
  • HLA-B Antigens / immunology
  • Humans
  • Interferon-gamma / immunology
  • Leukocytes, Mononuclear / immunology
  • Lipopeptides / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Models, Molecular
  • Polymorphism, Genetic
  • Protozoan Proteins / immunology*
  • Protozoan Vaccines / immunology*
  • Toxoplasma / immunology
  • Toxoplasmosis / genetics*
  • Toxoplasmosis / immunology
  • Toxoplasmosis, Congenital / genetics
  • Toxoplasmosis, Congenital / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, Protozoan
  • Epitopes, T-Lymphocyte
  • GRA3 protein, Toxoplasma gondii
  • GRA6 protein, Toxoplasma gondii
  • GRA7 protein, Toxoplasma gondii
  • HLA-A Antigens
  • HLA-B Antigens
  • Lipopeptides
  • Minor Histocompatibility Antigens
  • Protozoan Proteins
  • Protozoan Vaccines
  • SAG1 antigen, Toxoplasma
  • Interferon-gamma
  • Aminopeptidases
  • ERAP1 protein, human
  • ERAP2 protein, human