Basic research for the development of peptide vaccination against Hepatitis C virus infection

丙型肝炎病毒感染肽疫苗开发的基础研究

• 批准号: 18590756
• 负责人: YAMADA Akira
• 金额: $ 2.57万
• 依托单位: Kurume University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590756/
• 关键词: Virus; Infectious Disease; Immunology

Identification of CTL-epitope peptides: We selected and synthesized 44 9-mer or 10-mer peptides that were theoretically bind to HLA-A24 molecule from HCV1 b-derived protein by in silico analysis. We further picked up 6 peptides by patients' IgG antibody screening from the 44 peptides and CTL-inducing activity of the 6 peptides were subsequently examined using HCV-infected patients' peripheral blood mononuclear cells. Finally, we identified 3 peptides that are able to induce CTL in HLA-A24 patients (Hepatology Research, 2007). We also identified HLA-A3 supertype-restricted CTL-epitope peptides using similar strategy. Namely, we selected 46 peptides that were theoretically bind to HLA-A3 supertype (HLA-A3, -All, -A31, -A33) molecule from HCV1 b proteins by in silico analysis and finally 3 peptides that are able to induce CTL in HLA-A3 supertype patients were identified (Cancer Immunology Immunotherapy, 2007). The HLA-A2, -A24, and -A3 supertype are found in 40%, 60%, and 44%, respectivel … More y, of Japanese. Therefore, the previously identified vaccine candidate peptides for HLA-A2, together with the newly identified peptides for HLA-A24 and-A3 supertype patients, are able to cover the majority of HCV1 b patients in Japan.Anti-HCV peptide antibody as bio-marker: Relationship between serum IgG antibodies reactive to the CTL-epitope peptides and clinical status of HCV1 b-infected patients was analyzed. The serum IgG levels reactive to Core 35-44 peptide were found to correlate, with disease progression, such as progression from chronic hepatitis to liver cirrhosis or hepatocellular carcinoma. In contrast, the serum IgG levels to NS5A 2132-2142 peptide expressed reverse correlation to the disease progression (Med. Microbiol. Immunol., 2007).Clinical trial of peptide vaccination: To assess the safety and immune responses to a peptide vaccination of HCV1 b-derived peptides, 12 HCV1 b-positive patients, who were unresponsive to interferon-based therapy, were enrolled in the trial and safety and immunological effects of the vaccination were confirmed (Vaccine, 2007). Less

CTL-eppetope Petides的鉴定：我们通过在硅硅分析中从HCV1 B衍生的蛋白质中选择并合成了44个9-9-MER或10-MER PETIDE与HLA-A24分子结合。我们进一步从44例Petides的IgG抗体筛选和CTL诱导的6种PETIDE的活性中进一步挑选了6个PETIDE，随后使用HCV感染的患者的外周血单核细胞检查了6个Petides。最后，我们确定了3种能够在HLA-A24患者中诱导CTL的肽（Hepatology Research，2007年）。我们还使用类似的策略确定了HLA-A3超构型限制的CTL-EPPETOPE肽。 Namely, we selected 46 peptides that were theoretical bind to HLA-A3 supertype (HLA-A3, -All, -A31, -A33) molecule from HCV1 b proteins by in silico analysis and finally 3 peptides that are able to Induce CTL in HLA-A3 supertype patients were identified (Cancer Immunology Immunotherapy, 2007). HLA -A2，-A24和-A3超构型的40％，60％和44％，相对……更多的日语。 Therefore, the previously identified vaccine candidate peptides for HLA-A2, together with the newly identified peptides for HLA-A24 and-A3 supertype patients, are able to cover the majority of HCV1 b patients in Japan.Anti-HCV pepper antibody as bio-marker: Relationship between serum IgG antibodies reactive to the CTL-epitope peptides and clinical status of HCV1分析了B感染的患者。发现血清IgG水平反应至35-44肽与疾病进展相关，例如从慢性肝炎到肝肝硬化或肝细胞癌的进展。相反，NS5A 2132-2142肽的血清IgG水平与疾病进展相反（Med。Microbiol。Immunol。，2007）。肽疫苗的临床试验：评估对HCV1 B衍生肽的肽疫苗的安全性和免疫回应，对基于Interferon的疗法无反应的12名HCV1 B阳性患者已招募了疫苗的试验，安全和免疫学作用。较少的

项目成果

Identification of hepatitis C virus (HCV) 2a-serived epitope peptides having the capacity to induce cytotoxic T lymphocytes in human leukocyte antigen-a24^+ and HCV2a-infected patients.

鉴定具有在人白细胞抗原-a24 和HCV2a感染的患者中诱导细胞毒性T淋巴细胞的能力的丙型肝炎病毒(HCV)2a-服务的表位肽。

• 发表时间: 2006
• 期刊: Cell.Immunol, 241・1
• 作者: Komohara Y;Yamada A;et. al.;Morimoto H;Y Wang.
• 通讯作者: Y Wang.

Serum levels pf IgG to the peptide of HCV-1b core at positions 35-44 correlated with persistent infection, while levels FIgG to the peptide of NS5A at position 2131-2140 correlated with better prognosis in HCV-infected patients.

HCV-1b核心35-44位的肽的血清IgG水平与持续感染相关，而NS5A 2131-2140位的肽的FIgG水平与HCV感染患者更好的预后相关。

• 期刊: Medical Microbiol.Immunol. (In Press)
• 作者: 小林 聡;伊勢裕彦;他;Takao Y.
• 通讯作者: Takao Y.

Phase 1 clinical study of a personalized peptide vaccination for patientsinfected with hepatitis C virus(HCV) lb who failed to respond to interferon-based therapy.

针对感染丙型肝炎病毒 (HCV) 1b 对干扰素治疗无反应的患者进行个性化肽疫苗接种的 1 期临床研究。

• 发表时间: 2007
• 期刊: Vaccine 25(42)
• 作者: Yutani S;Yamada A;et. al.
• 通讯作者: et. al.

「研究成果報告書概要(和文)」より

摘自《研究结果报告摘要（日文）》

• 发表时间: 2005
• 作者: Kawauchi;et. al.;Nishimura et al.;Dezawa et al.;Yoshizawa et al.;星野 幹雄;星野 幹雄
• 通讯作者: 星野 幹雄

C型肝炎ウィルス由来ペプチド

丙型肝炎病毒衍生肽

• 发表时间: 2005