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

Tze Guan Tan, Ernest Mui, Hua Cong, William H. Witola, Alexandre Montpetit, Stephen P. Muench, John Sidney, Jeff Alexander, Alessandro Sette, Michael E. Grigg, Ajesh Maewal, Rima McLeod

Research output: Contribution to journalArticlepeer-review

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 Ld mice with HF10 (HPGSVNEFDF) with palmitic acid moieties or a monophosphoryl lipid A derivative elicited potent IFN-γ production from Ld-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.

Original languageEnglish (US)
Pages (from-to)3977-3989
Number of pages13
JournalVaccine
Volume28
Issue number23
DOIs
StatePublished - May 21 2010
Externally publishedYes

Keywords

  • HLA Class 1 bound peptides
  • Toxoplasma gondii
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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