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中国科学院生物物理研究所,生物大分子全国重点实验室副主任,研究组长
2009 四川大学生物技术专业,获得理学学士学位
2014 中国科学院生物物理研究所,获得理学博士学位
2014.07 - 2014.09 中国科学院生物物理研究所,副研究员
2014.09 - 2016.02 牛津大学,访问学者
2014.10 - 至今 中国科学院生物物理研究所,研究员
2014年 吴瑞奖学金
2014年 中国科学院青年研究员人才计划
2015年 青年人才托举工程
2015年 贝时璋青年生物物理学家奖
2020年 中国科学院青年科学家奖
2020年 中源协和生命医学创新奖
2021年 首届钟南山青年科技创新奖
2021年 谈家桢生命科学创新奖
2022年 TR35青年创新奖
2022年 第十七届中国青年科技奖
2023年 第六届中国转化医学奖
2024年 中央和国家机关青年五四奖章
本课题组主要研究方向包括以下三方面:
1. 冠状、流感等极易突变型病毒的免疫机制研究、抗体谱系解析和广谱疫苗开发
冠状病毒、流感病毒等高度易突变病毒可通过抗原漂移或转换逃逸宿主免疫识别,削弱传统疫苗的保护效力,因此亟待新型广谱型疫苗以建立有效的人群免疫屏障。自然感染或疫苗接种后,病毒在机体的体液免疫驱动下发生定向进化,通过更新突变株或转换主要流行株等方式继续实现宿主共存。抗体谱系分析可揭示中和抗体的发育路径、靶向表位及广谱识别机制,为优化疫苗保护性抗原设计提供依据。
本课题组针对高度突变病毒的疫苗研发,结合了结构生物学、病毒学、免疫学和生物信息学,通过调控抗原特异性/广谱性免疫信号改造免疫原,以诱导强效、广谱中和抗体。同时利用新型疫苗技术(如mRNA、纳米颗粒等)来提高免疫原性及保护周期。此外,利用基于AI的抗原改造定向调控免疫原诱导的中和抗体谱系,优先激活成熟广谱抗体,提高交叉保护效力,为"通用疫苗"研发奠定基础。
2. 登革病毒/呼吸道合胞病毒等ADE/VAERD型病毒的免疫机制研究、抗体谱系解析和中和抗体与新型疫苗开发
DENV和RSV等病毒可通过ADE或VAERD加剧疾病进程,使得基于传统路线开发的疫苗易引发严重的安全问题。DENV的四种血清型可诱导非中和交叉抗体,在异型病毒二次感染时促进病毒复制并加重疾病,而RSV早期灭活疫苗接种导致严重的免疫病理反应,其表面抗原的非保护性表位可能是关键诱因。
本课题组聚焦于ADE/VAERD型病毒的免疫机制解析、抗体谱系追踪及安全性疫苗设计。通过高通量单细胞测序、深度突变扫描等技术,系统解析DENV和RSV不同时空背景自然感染及疫苗接种人群诱导的中和抗体谱系规律,识别导致ADE/VAERD的不良免疫信号和关键保护性表位。结合结构生物学与AI蛋白设计技术,稳定保护性抗原构象,屏蔽ADE不良信号,使免疫原诱导亲和力高、ADE风险低的强效中和抗体,同时避免非中和抗体的产生,从而为安全、高效的DENV及RSV疫苗研发提供理论基础和技术支持,推动突破长期困扰人类的疫苗安全性难题。
3. 非洲猪瘟病毒、疱疹病毒等成分复杂型病原体保护性抗原谱破译和强效保护性疫苗开发
非洲猪瘟病毒(ASFV)拥有近200个编码基因,其高度复杂的衣壳和包膜蛋白影响疫苗诱导的免疫应答。本课题组解析ASFV的保护性抗原表位及其介导的体液和细胞免疫机制,有助于筛选关键免疫原,避免诱导非保护性免疫反应。疱疹病毒如HCMV、VZV、HSV-2等可长期潜伏于宿主体内,周期性激活并逃避免疫清除。本课题组基于高通量免疫学手段解析感染人群血清抗体谱系,鉴定保护性抗原集合并通过AI蛋白质设计技术开发多价疫苗。同时,利用自主知识产权的VLP与免疫原仿生展示技术,构建纳米颗粒疫苗,刺激机体诱导强效、持久的体液免疫。
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(资料来源:王祥喜研究员,2025-02-19)