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表位肽的鉴定：我们通过计算机模拟分析，从HCV 1b衍生蛋白中选择并合成了44个理论上与HLA-A24分子结合的9-mer或10-mer肽。我们进一步通过患者的IgG抗体筛选从44种肽中挑选出6种肽，随后使用HCV感染患者的外周血单个核细胞检测6种肽的CTL诱导活性。最后，我们鉴定了能够在HLA-A24患者中诱导CTL的3种肽（Hepatology Research，2007）。我们还使用类似的策略鉴定了HLA-A3超型限制性CTL表位肽。即，我们通过计算机模拟分析从HCV 1 B蛋白中选择了理论上与HLA-A3超型（HLA-A3，-A11，-A31，-A33）分子结合的46种肽，并最终鉴定了能够在HLA-A3超型患者中诱导CTL的3种肽（Cancer Immunology Immunotherapy，2007）。HLA-A2、-A24和-A3超型分别占40%、60%和44%。 ...更多信息 ，日本人。因此，先前鉴定的HLA-A2的疫苗候选肽，连同新鉴定的HLA-A24和HLA-A3超型患者的肽，能够覆盖日本的大多数HCV 1 B患者。抗HCV肽抗体作为生物标志物：分析与CTL表位肽反应的血清IgG抗体与HCV 1 b感染患者的临床状态之间的关系。发现与核心35-44肽反应的血清IgG水平与疾病进展相关，例如从慢性肝炎进展为肝硬化或肝细胞癌。相比之下，针对NS 5A 2132-2142肽的血清IgG水平表达与疾病进展的负相关性（Med.Microbiol.免疫学，2007).肽疫苗接种的临床试验：为了评估对HCV 1b衍生肽的肽疫苗接种的安全性和免疫应答，将12名对基于干扰素的治疗无应答的HCV 1b阳性患者纳入试验，并证实了疫苗接种的安全性和免疫学效果（Vaccine，2007）。少

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 of IgG to the peptide of HCV-1b core at positions 35-44 correlated with persistent infection, while levels of IgG to the peptide of NS5A at position 2132-2140 correlated with better prognosis in HCV-infected patients.

HCV-1b核心第35-44位肽的IgG水平与持续感染相关，而NS5A第2132-2140位肽的IgG水平与HCV感染患者更好的预后相关。

• 发表时间: 2007
• 期刊: Medical Microbiol.Immunol. (In press)
• 作者: Takao Y;Itoh K;et al.
• 通讯作者: et al.

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.

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 patients infected with hepatitis C virus (HCV) 1b who failed to respond to interferon-based therapy

针对感染丙型肝炎病毒 (HCV) 1b 且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
• 作者: Yutani S;et. al.
• 通讯作者: et. al.