Towards an immunosense vaccine to prevent toxoplasmosis: Protective Toxoplasma gondii epitopes restricted by HLA-A*0201

被引:42
作者
Cong, Hua [2 ,3 ]
Mui, Ernest J. [2 ]
Witola, William H. [2 ]
Sidney, John [4 ]
Alexander, Jeff [5 ]
Sette, Alessandro [4 ]
Maewal, Ajesh [6 ]
McLeod, Rima [1 ,7 ,8 ,9 ,10 ,11 ]
机构
[1] Univ Chicago, Inst Genom & Syst Biol & Coll, Comm Immunol, Dept Surg Ophthalmol, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Surg, Chicago, IL 60637 USA
[3] Shandong Univ, Dept Parasitol, Sch Med, Jinan 250012, Shandong, Peoples R China
[4] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA
[5] Pharmexa Epimmune, San Diego, CA 92121 USA
[6] Synthet Biomol, San Diego, CA 92121 USA
[7] Univ Chicago, Inst Genom & Syst Biol & Coll, Comm Mol Med, Dept Surg Ophthalmol, Chicago, IL 60637 USA
[8] Univ Chicago, Inst Genom & Syst Biol & Coll, Comm Genet, Dept Surg Ophthalmol, Chicago, IL 60637 USA
[9] Univ Chicago, Inst Genom & Syst Biol & Coll, Comm Immunol, Dept Pediat Infect Dis, Chicago, IL 60637 USA
[10] Univ Chicago, Inst Genom & Syst Biol & Coll, Comm Mol Med, Dept Pediat Infect Dis, Chicago, IL 60637 USA
[11] Univ Chicago, Inst Genom & Syst Biol & Coll, Comm Genet, Dept Pediat Infect Dis, Chicago, IL 60637 USA
基金
中国国家自然科学基金;
关键词
Toxoplasma gondii; HLA-A2; epitope; Vaccine; IFN-GAMMA; FUNCTIONAL-CHARACTERIZATION; OCULAR TOXOPLASMOSIS; T-CELLS; SURFACE; BINDING; RESPONSES; PEPTIDES; AFFINITY; INFECTION;
D O I
10.1016/j.vaccine.2010.11.015
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-gamma-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-gamma 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-gamma production and protected against parasite challenge. Peptides identified in this study provide candidates for inclusion in immunosense epitope-based vaccines. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:754 / 762
页数:9
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