Investigation for the development of vaccine against hepatitis C virus

丙型肝炎病毒疫苗的研制研究

• 批准号: 09670515
• 负责人: MARUYAMA Toshiyuki
• 金额: $ 1.98万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670515/
• 关键词: HCV; peptide; vaccine; interferon; IgG subtype; prognostic ralue; mouse; エペトープ; IgGサブクラス; C型肝炎; ペプタイト; 免疫応答

We have examined the murine T cell response to HCV core protein in terms of immunogenicity, the influence of H-2 linked genes, fine specificity, and relationship to in vivo antibody production by using recombinant HCV core protein which contains full length of entire core region. The HCV core protein was shown to have markedly lower immunogenicity compared to HBcAg on humoral and cellular response. The influence of H-2 linked genes on the humoral response to HCV core protein was discernible, and high responder (H-2f), intermediate responder (H-2b, s), and low responder (H-2k, d, p) haplotypes were identified. T cell recognition sites were defined by small (18 residue) synthetic peptides. Each strain recognized a predominant T cell determinant, and the fine specificity of this recognition process was dependent on the H-2 haplotype of the responding strain. For example, H-2f strain recognized p41-55, H-2b strain recognized p11-25, H-2s strain recognized p161-175 predominantly. When B10.M (H2-f) mice were primary immunized by p41-55 peptide, these mice had enough immune response after secondary immunization with HCV core protein. Therefore, p41-55 peptide is a good candidate for vaccine against HCV infection. These results that immune response to HCV core antigen is influenced by H-2 linked genes and that HCV core antigen is low immunogenic have clinical relevance most of patients with acute HCV infection produce lower antibodies against viral proteins in early phase.

我们已经研究了小鼠T细胞对HCV核心蛋白的免疫原性，H-2连接基因的影响，良好的特异性，以及与体内抗体产生的关系，通过使用重组HCV核心蛋白，其中包含整个核心区的全长。在体液和细胞应答方面，HCV核心蛋白的免疫原性明显低于HBcAg。H-2连锁基因对HCV核心蛋白体液应答的影响是可辨别的，并且鉴定出高应答（H-2f）、中等应答（H-2b，s）和低应答（H-2k，d，p）单倍型。T细胞识别位点由小（18个残基）合成肽限定。每个菌株识别一个占主导地位的T细胞决定簇，这种识别过程的精细特异性取决于响应菌株的H-2单倍型。如H-2f株主要识别p41-55，H-2b株主要识别p11-25，H-2s株主要识别p161-175。用p41-55肽初次免疫B10.M（H2-f）小鼠，用HCV核心蛋白二次免疫后，这些小鼠有足够的免疫应答。因此，p41-55肽是一个很好的候选疫苗抗HCV感染。HCV核心抗原的免疫应答受H-2连锁基因的影响，HCV核心抗原的免疫原性较低，这一结果具有临床意义。

项目成果

T.Maruyama: "Precore Wild type DNA and immune complexes persisl in chronic hepatitis B after seroconversion" Hepatology. 27. 245-253 (1998)

T.Maruyama：“Precore 野生型 DNA 和免疫复合物在血清转化后慢性乙型肝炎中持续存在”肝病学。

T. Maruyama. et al.: "High prevalence of pre-c wild type HBV-DNA and HBeAg/ICs in patients with chronic hepatis B often seroconversion."Hepatology. 27. 245-253 (1998)

T·丸山。

K.Koike,et al: "Sialadenitis resembling Sjogren's syndrome in hepatitis C virus envelope gene transgenic mice." Proc Natl Acad Sci USA. 94. 233-236 (1997)

K.Koike 等人：“丙型肝炎病毒包膜基因转基因小鼠中的唾液腺炎类似于干燥综合征。”

Mitsui H,: "Thrombin activates two stress-activated protein kinases" Hepatology. 27. 1362-1367 (1998)

Mitsui H，：“凝血酶激活两种应激激活蛋白激酶”肝病学。

H. Mitsui. et al.: "Thrombin activates two stress-activated protein kinases, c-jun, N terminal kinase and p38 in Hep G2 cells"Hepatology. 27. 1362-1367 (1998)

H.三井。