Department of Surgery, The University of Chicago, 5841 S. Maryland Ave., MC 2114, Chicago, IL 60637, USA.
Vaccine. 2011 Jan 17;29(4):754-62. doi: 10.1016/j.vaccine.2010.11.015. Epub 2010 Nov 21.
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.
理想的弓形虫病人类疫苗应包括能引发保护性辅助性 T 细胞 1 型免疫应答并产生长寿命 IFN-γ产生 CD8(+)T 细胞的抗原。在此,我们利用预测算法从弓形虫蛋白中鉴定候选 HLA-A02 超型表位。13 种肽可从 HLA-A02 超型人 PBMC 中诱导 IFN-γ产生,这些人对 T. gondii 感染呈血清阳性,但对血清阴性对照无反应。这些肽与 HLA-A02 蛋白具有高亲和力结合。用佐剂 GLA-SE 配制通用 CD4(+)表位肽 PADRE,用这些混合肽免疫 HLA-A*0201 转基因小鼠,可诱导 CD8(+)T 细胞 IFN-γ产生并预防寄生虫攻击。本研究中鉴定的肽为包含在免疫感觉表位为基础的疫苗候选物。