金葡菌疫苗抗原Hla及IsdB的HLA-DR限制性Th17细胞优势表位的鉴定及其免疫保护机制研究
结题报告
批准号:
31970869
项目类别:
面上项目
资助金额:
50.0 万元
负责人:
赵卓
学科分类:
疫苗、抗体与免疫干预
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
赵卓
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中文摘要
耐甲氧西林的金黄色葡萄球菌(金葡菌)感染危害严重,研制有效的疫苗来防控其感染已迫在眉睫。抗原诱发的Th17细胞应答对抗金葡菌感染具有重要作用。本团队研发的五价金葡菌疫苗动物保护率高,已进入II期临床人群试验,发现:疫苗抗原溶血素α(Hla)及铁离子表面决定蛋白(IsdB)在人群中诱发了显著的Th17细胞应答,部分免疫者之间,分泌IL-17水平有差异;在HLA-DR基因型不同的MRSA感染者中,Hla及IsdB的Th17细胞应答优势表位不同。本项目拟从“表位优势应答和HLA限制性”层面,在疫苗免疫人群及MRSA感染者,系统分析Hla及IsdB的Th17细胞优势应答表位及其HLA-DR限制性,研究表位保护性及表位特异性CD4+T细胞表型特征,分析其免疫保护机制,为深入揭示Hla及IsdB的抗金葡菌感染的免疫保护机制提供新的线索,为精细解析金葡菌疫苗抗原在人群免疫中的有效作用分子提供理据。
英文摘要
Methicillin-resistant Staphylococcus aureus (MRSA) is multiple drug-resistant causing serious damage with high infection rate. The Th17 cell response plays an important role in fighting against Staphylococcus aureus infection. We have developed a pentavalent vaccine that could fight well against Staphylococcus aureus infection. This vaccine study has entered the phase II clinical population trials, in which both Hla (alpha-Hemolysin) and IsdB (Iron-regulated surface determinant B) have induced significant antigen-specific Th17 cell response. The levels of IL-17 secreted by antigen-specific CD4+T cells were significantly different among some immunized individuals. Hla and IsdB could induce Th17 cell responses with different immunodominant-epitope spectrum in MRSA infected individuals with different HLA-DR genotypes. Therefore, on the level of "the dominant epitope response and HLA genotype restriction",this project aims to identify the dominant epitope inducing responses in Hla and IsdB specific Th17 cell responses in the immunized individuals and MRSA infected individuals. We will analyze the HLA-DR genotype restriction for the specific epitope response, will identify the phenotypic characteristics of those epitope specific CD4+T cells, and will also study the protective mechanism of the immunodominant-epitope response. This study will finely analyze the protective mechanism of Hla and IsdB inducing response against Staphylococcus aureus infection, and will also finely analyze the effective molecules in the Staphylococcus aureus vaccine antigens in the immunized individuals.
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DOI:10.2147/jir.s325286
发表时间:2021
期刊:Journal of inflammation research
影响因子:4.5
作者:Duan L;Zhang J;Chen Z;Gou Q;Xiong Q;Yuan Y;Jing H;Zhu J;Ni L;Zheng Y;Liu Z;Zhang X;Zeng H;Zou Q;Zhao Z
通讯作者:Zhao Z
DOI:--
发表时间:2023
期刊:Immunotherapy
影响因子:2.8
作者:Sisi Li;Lianli Duan;Xiaoli Zhang;Rui Yang;Longlong Chen;Zhifu Chen;Qiang Gou;Wenxin Bao;Yue Yuan;Haiming Jing;Yi Zhang;Ping Cheng;Ping Luo;Li Ni;Wanneng Wang;Zhuo Zhao
通讯作者:Zhuo Zhao
DOI:10.3389/fimmu.2021.684823
发表时间:2021
期刊:Frontiers in immunology
影响因子:7.3
作者:Chen Z;Gou Q;Xiong Q;Duan L;Yuan Y;Zhu J;Zou J;Chen L;Jing H;Zhang X;Luo P;Zeng H;Zou Q;Zhao Z;Zhang J
通讯作者:Zhang J
DOI:10.1093/infdis/jiaa602
发表时间:2021-05-15
期刊:JOURNAL OF INFECTIOUS DISEASES
影响因子:6.4
作者:Zeng, Hao;Zhang, Jinyong;Zhao, Zhuo
通讯作者:Zhao, Zhuo
新冠病毒表位的HLA-DR限制性Th优势应答谱学特征及其与疾病转归相关性研究
金黄色葡萄球菌肠毒素B的B细胞免疫优势表位的鉴定及免疫保护机制研究
国内基金
海外基金