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Towards an immunosense vaccine to prevent toxoplasmosis: protective Toxoplasma gondii epitopes restricted by HLA-A*0201 |
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| Authors: | Cong Hua Mui Ernest J Witola William H Sidney John Alexander Jeff Sette Alessandro Maewal Ajesh McLeod Rima |
| Affiliation: | a Department of Surgery, The University of Chicago, 5841 S. Maryland Ave., MC 2114, Chicago, IL 60637, USA b Department of Parasitology, School of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012, China c Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA d Pharmexa-Epimmune, San Diego, CA 92121, USA e Synthetic Biomolecules, 9863 Pacific Heights Blvd., Suite F, San Diego, CA 92121, USA f Departments of Surgery (Ophthalmology) and Pediatrics (Infectious Disease), Committees on Immunology, Molecular Medicine, and Genetics, Institute of Genomics and Systems Biology, and The College, The University of Chicago, 5841 S. Maryland, Ave., MC 2114, Chicago, IL 60637, USA |
| 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. |
| Keywords: | Toxoplasma gondii HLA-A2 epitope Vaccine |
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