基于血凝素广谱中和抗体C12G6的乙型流感通用疫苗设计研究
结题报告
批准号:
32000649
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
陈俊煜
依托单位:
学科分类:
疫苗、抗体与免疫干预
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
陈俊煜
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中文摘要
流感病毒是危害人类健康的重要呼吸道病毒。血凝素HA是流感病毒诱导机体产生保护性抗体的主要抗原。近年来研究发现HA存在广谱中和表位,为研发长期有效的通用流感疫苗带来希望,但这些广谱表位多是非连续的构象依赖性表位,如何将构象表位理性设计成有效的免疫原成为疫苗研究的共性难题。项目组前期研究发现一个乙型流感广谱中和抗体C12G6,并解析出C12G6表位的晶体结构,本研究拟通过突变分析确定C12G6表位多肽区段,尝试用多种表达载体构建C12G6表位疫苗,同时尝试用基于Rosetta系统的计算分析方法对C12G6表位疫苗进行理性设计,构建出最优化的C12G6表位疫苗,最后通过一系列疫苗抗原性和免疫原性评价及结构解析验证,为基于构象性广谱表位的乙型流感通用疫苗研究提供理性设计规则和科学依据。
英文摘要
Influenza viruses were critical respiratory viruses, which caused severe threaten in humans as a serious public health problem. Hemagglutinin (HA) is the most significant glycoprotein in influenza surface and the major target for host immune response. In recent years, broadly neutralizing antibodies against the conserved epitopes of influenza virus HA isolated and identified, which promoting the foundation for newly vaccine development. Generally, the epitope targeted by broadly neutralizing antibodies in HA surface were conformational and discontinuous but poorly immunogenic. The study had been critical scientific problem for universal influenza vaccine research about rational vaccine design for immune focusing on broadly neutralizing epitopes by structural basis for conformation-independent epitopes. According to the previous analysis of the crystal structure of C12G6-HA complex, the epitope peptide recognized by C12G6 was screened and selected for further epitope vaccines design based on structural biology. In this study, the epitope peptides recognized by C12G6 which confirmed by mutation screening were fused to traditional expression carrier for epitopes vaccines at first. On the other hand, we aims to design immunogen for resurfacing the epitopes in vitro by scaffold design of Rosetta system. After the evaluation of antigenicity and immunogenicity, immunogen structure were also identified and analyzed for the most optimized candidate epitope vaccine, which would provide structural basis and theory guide for universal influenza B virus vaccine design based on conformational broadly neutralizing epitopes.
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DOI:10.3390/v14061305
发表时间:2022-06-14
期刊:Viruses
影响因子:--
作者:
通讯作者:
DOI:10.1038/s41467-022-32926-5
发表时间:2022-09-02
期刊:Nature communications
影响因子:16.6
作者:
通讯作者:
Vaccination with Deglycosylated Modified Hemagglutinin Broadly Protects against Influenza Virus Infection in Mice and Ferrets.
去糖基化修饰血凝素疫苗可广泛保护小鼠和雪貂免受流感病毒感染
DOI:10.3390/vaccines10081304
发表时间:2022-08-11
期刊:VACCINES
影响因子:7.8
作者:Zhang, Limin;Chen, Junyu;Shen, Chenguang;Wang, Guosong;Lu, Zhen;Zeng, Dian;Gao, Ying;Chen, Huiqing;Xia, Ningshao;Chen, Yixin
通讯作者:Chen, Yixin
国内基金
海外基金