title: Towards an immunosense vaccine to prevent toxoplasmosis: protective Toxoplasma gondii epitopes restricted by HLA-A*0201.
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.
authors.affiliation: Department of Surgery, The University of Chicago, 5841 S. Maryland Ave., MC 2114, Chicago, IL 60637, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Cong
authors.forename: Ernest J
authors.initials: EJ
authors.lastname: Mui
authors.forename: William H
authors.initials: WH
authors.lastname: Witola
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Jeff
authors.initials: J
authors.lastname: Alexander
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Ajesh
authors.initials: A
authors.lastname: Maewal
authors.forename: Rima
authors.initials: R
authors.lastname: McLeod
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D014122:Toxoplasma / Q000235:genetics / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D007371:Interferon-gamma