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

Vaccine. 2010 Mar 25. [Epub ahead of print]

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

Tan TG, Mui E, Cong H, Witola W, Montpetit A, Muench SP, Sidney J, Alexander J, Sette A, Grigg M, Maewal A, McLeod R.

Department of Surgery, Committees on Immunology, Molecular Medicine, and Genetics, Institute of Genomics and Systems Biology, and The College, The University of Chicago, Chicago, IL 60615, USA; Department of Pediatrics (Infectious Disease), Committees on Immunology, Molecular Medicine, and Genetics, Institute of Genomics and Systems Biology, and The College, The University of Chicago, Chicago, IL 60615, USA.

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. Copyright © 2010. Published by Elsevier Ltd.

PMID: 20347630 [PubMed - as supplied by publisher]