Journal
VACCINE
Volume 28, Issue 23, Pages 3977-3989Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.03.028
Keywords
Toxoplasma gondii; Vaccine; HLA Class 1 bound peptides
Categories
Funding
- Fin Charity Trust
- Dominique Cornwell and Peter Mann Family Foundation
- Intervet/Schering Plough
- Toxoplasmosis Research Institute
- DMID-NIAID [U01 A177887]
- NIH, NIAID
- The Research to Prevent Blindness Foundation
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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. (C) 2010 Elsevier Ltd. All rights reserved.
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