Development of T-cell vaccine for hepatitis C virus

丙型肝炎病毒T细胞疫苗的开发

• 批准号: 07557047
• 负责人: IMAWARI Michio
• 金额: $ 6.14万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557047/
• 关键词: hepatitis C virus; hepatitis C; cytotoxic T cell; DNA vaccine; GM-CSF; ヘルパーT細胞; HLAB44; ワクチン; インターロイン12

We tried to develop T-cell vaccine to prevent and treat hepatitis C virus (HCV) infection. We established cytotoxic T cell clones from peripheral blood lymphocytes of two HLA B44-positive patients with chronic HCV infection that recognize HCV core antigen 88-96 as a minimal and optimal epitope. We demonstrated that positions 4 and 6 of the 9 amino acid epitope were important for the binding of the epitope and T-cell antigen receptors of the CTL clones. When amino acids at positions 4 and 7 were substituted by other amino acids, a wild type epitope for type 1b and 2a HCV (NEGLGWAGW) and a variant type for 2b HCV (NEGCGWMGW) were recognized most efficitntly by CTL slones. HCV DNA that express HCV core antigen in the tranfected mammalian cells induced HCV-specific CTL when the DNA was injected directly into the spleen of mice. Intramuscular injection of the DNA did not induce CTL in either mice or chimpanzees.

我们试图开发T细胞疫苗，以预防和治疗丙型肝炎病毒（HCV）感染。我们从两名HLA B44阳性HCV感染的HLA B44阳性患者的外周血淋巴细胞中建立了细胞毒性T细胞克隆，这些HLA B44阳性患者识别HCV核心抗原88-96是最小和最佳表位。我们证明了9个氨基酸表位的位置4和6对于CTL克隆的表位和T细胞抗原受体的结合至关重要。当位置4和7处的氨基酸被其他氨基酸取代时，野生型表位1B和2A HCV（NEGLGWAGW）和2B HCV（negcgwmgw）的变体类型被CTL Slones认识到最效率。当将DNA直接注入小鼠的脾脏时，在三培养的哺乳动物细胞中表达HCV核心抗原的HCV DNA诱导HCV特异性CTL。肌内注射DNA不会在小鼠或黑猩猩中诱导CTL。

项目成果

Ando,Kazuki: "Perforin,Fas/Fas Ligand,TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL" Journal of Immunology. 158. 5283-5291 (1997)

Ando，Kazuki：“穿孔素、Fas/Fas 配体、TNF-α 途径作为丙型肝炎病毒特异性人类 CTL 的特异性和旁观者杀伤机制”《免疫学杂志》158. 5283-5291 (1997)。

Ando,Kazuki: "Perfporin,Fas/Fas ligand,TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL" Journal of Immunology. (印刷中). (1997)

Ando，Kazuki：“Perfporin、Fas/Fas 配体、TNF-α 途径作为丙型肝炎病毒特异性人类 CTL 的特异性和旁观者杀伤机制”（正在出版）。

Hiroishi,Kazumasa: "Cytotoxic T lymphocyte response and viral load in hepatitis C virus infection" Hepatology. 25(印刷中). (1997)

Hiroishi, Kazumasa：“丙型肝炎病毒感染中的细胞毒性 T 淋巴细胞反应和病毒载量”《肝病学》25（出版中）。