疫苗与结构生物学组

(一)本组简介

人员构成:教师3人、工程师1人、博士后1人,学生33人、技术员8人,共46人。

研究方向:基因工程疫苗研究与开发、重要传染病病毒免疫表位的结构和功能研究、基于结构的分子模拟和分子设计。

技术平台:基因工程疫苗研发平台、基于CRISPR-Cas9技术的大肠杆菌基因组改造、杆状病毒表达系统、哺乳动物细胞表达系统、X-ray衍射晶体结构解析平台、Cryo-EM结构解析平台、分子动力学计算平台、二代测序平台。

研究内容:

HPV系列:基于结构的人乳头病毒(HPV)型交叉疫苗研发、HPV抗体中和机制研究、HPV 主要衣壳蛋白L1与次要衣壳蛋白L2相互作用研究、L2蛋白结构研究、HPV致癌蛋白的功能机制研究;

HEV系列:戊型肝炎病毒(HEV) 广谱中和抗体和型特异抗体表位及机制研究;HEV结构为基础设计的通用的颗粒化疫苗研究;

流感、肠道病毒等的结构研究:解析流感的血凝素蛋白(HA)和肠道病毒多种衣壳形式与中和抗体的复合物结构,研究抗体介导的病毒中和作用机制;

疫苗质量控制: 疫苗相关质量分析方法的建立、生物药物后期转化;

新型佐剂: 新型佐剂筛选、佐剂及抗原-佐剂间的相互作用分析、佐剂机制探索。

(二)导师

李少伟、赵勤俭、俞海

(三)正在开展的项目

1.HEV/HPV多价联合疫苗研究与产品开发  

2.肠道病毒抗原性差异的结构基础  

3.基因工程疫苗研发和生产用的大肠杆菌表达系统的基因组功能改造和应用  

4.基于结构的流感HA关键表位研究

5.新型佐剂筛选及机制研究

(四)近5年来发表的部分文章

1) Zheng, Q., R. Zhu, L. Xu, M. He, X. Yan, D. Liu, Z. Yin, Y. Wu, Y. Li, L. Yang, W. Hou, S. Li, Z. Li, Z. Chen, Z. Li, H. Yu, Y. Gu, J. Zhang, T. S. Baker, Z. H. Zhou, B. S. Graham, T. Cheng, S. Li and N. Xia (2019). "Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization." Nat Microbiol 4(1): 124-133.

2) Wang, K., L. Zhou, X. Zhang, C. Song, T. Chen, J. Li, M. Zheng, Y. Wang, Q. Zheng, Z. Zheng, H. Yu, T. Wu, Y. Gu, J. Zhang, Q. Zhao, S. Li and N. Xia (2019). "Hepatitis E vaccine candidate harboring a non-particulate immunogen of E2 fused with CRM197 fragment A." Antiviral Res 164: 154-161.

3) Chen, T., K. Wang, X. Chi, L. Zhou, J. Li, L. Liu, Q. Zheng, Y. Wang, H. Yu, Y. Gu, J. Zhang, S. Li and N. Xia (2019). "Construction of a bacterial surface display system based on outer membrane protein F." Microbial Cell Factories 18(1): 70.

4) Chen, S., X. Huang, Y. Li, X. Wang, H. Pan, Z. Lin, Q. Zheng, S. Li, J. Zhang, N. Xia and Q. Zhao (2019). "Altered antigenicity and immunogenicity of human papillomavirus virus-like particles in the presence of thimerosal." Eur J Pharm Biopharm 141: 221-231.

5) Li, Z., S. Song, M. He, D. Wang, J. Shi, X. Liu, Y. Li, X. Chi, S. Wei, Y. Yang, Z. Wang, J. Li, H. Qian, H. Yu, Q. Zheng, X. Yan, Q. Zhao, J. Zhang, Y. Gu, S. Li and N. Xia (2018). "Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity." Nat Commun 9(1): 5360.

6) Lin, Q., T. Li, Y. Chen, S. Y. Lau, M. Wei, Y. Zhang, Z. Zhang, Q. Yao, J. Li, Z. Li, D. Wang, Q. Zheng, H. Yu, Y. Gu, J. Zhang, H. Chen, S. Li and N. Xia (2018). "Structural Basis for the Broad, Antibody-Mediated Neutralization of H5N1 Influenza Virus." J Virol 92(17).

7) Wei, M., D. Wang, Z. Li, S. Song, X. Kong, X. Mo, Y. Yang, M. He, Z. Li, B. Huang, Z. Lin, H. Pan, Q. Zheng, H. Yu, Y. Gu, J. Zhang, S. Li and N. Xia (2018). "N-terminal truncations on L1 proteins of human papillomaviruses promote their soluble expression in Escherichia coli and self-assembly in vitro." Emerg Microbes Infect 7(1): 160.

8) Zhang, C., X. Huang, S. Chen, Y. Li, Y. Li, X. Wang, J. Tang, L. Xia, Z. Lin, W. Luo, T. Li, S. Li, J. Zhang, N. Xia and Q. Zhao (2018). "Epitope clustering analysis for vaccine-induced human antibodies in relationship to a panel of murine monoclonal antibodies against HPV16 viral capsid." Vaccine 36(45): 6761-6771.

9) Zhang, Z., M. He, S. Bai, F. Zhang, J. Jiang, Q. Zheng, S. Gao, X. Yan, S. Li, Y. Gu and N. Xia (2018). "T = 4 Icosahedral HIV-1 Capsid As an Immunogenic Vector for HIV-1 V3 Loop Epitope Display." Viruses 10(12).

10) Zhang, Z., L. Wang, S. Bai, J. Qiao, H. Shen, F. Huang, S. Gao, S. Li, S. Li, Y. Gu and N. Xia (2018). "Expression, Purification and Characterization of Hiv-1 Capsid Precursor Protein p41." Protein J 37(2): 194-202.

11) Zhang, Z., F. Zhang, S. Bai, J. Qiao, H. Shen, F. Huang, S. Gao, S. Li, Y. Gu and N. Xia (2018). "Characterization and epitope mapping of a panel of monoclonal antibodies against HIV-1 matrix protein." Biotechnol Appl Biochem 65(6): 807-815.

12) Zhu, R., L. Xu, Q. Zheng, Y. Cui, S. Li, M. He, Z. Yin, D. Liu, S. Li, Z. Li, Z. Chen, H. Yu, Y. Que, C. Liu, Z. Kong, J. Zhang, T. S. Baker, X. Yan, Z. Hong Zhou, T. Cheng and N. Xia (2018). "Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10." Sci Adv 4(9): eaat7459.

13) Zheng M, Jiang J, Zhang X, Wang N, Wang K, Li Q, Li T, Lin Q, Wang Y, Yu H, Gu Y, Zhang J, Li S*, Xia N. (2018) Characterization of capsid protein (p495) of hepatitis E virus expressed in Escherichia coli and assembling into particles in vitro. Vaccine. 36, 2104–2111.

14) Li Z, Wang D, Gu Y, Song S, He M, Shi J, Liu X, Wei S, Li J, Yu H, Zheng Q, Yan X, Baker T S, Zhang J, McLellan JS*, Li S*, Xia N*. (2017) Crystal Structures of Two Immune Complexes Identify Determinants for Viral Infectivity and Type-Specific Neutralization of Human Papillomavirus. MBio 8, 5

15) Xu L, Zheng Q, Li S, He M, Wu Y, Li Y, Zhu R, Yu H, Hong Q, Jiang J, Li Z, Li S, Zhao H, Yang L, Hou W, Wang W, Ye X, Zhang J, Baker T S, Cheng T*, Zhou ZH, Yan, X*, Xia, N*. (2017) Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody. Nat Commun 8, 505.

16) Pan H, Li Z, Wang J, Song S, Wang D, Wei M, Gu Y, Zhang J, Li S*, Xia N*. (2017) Bacterially expressed human papillomavirus type 6 and 11 bivalent vaccine: Characterization, antigenicity and immunogenicity., Vaccine 35, 3222–3231.

17) Wang D, Fan F, Li Z, Liu X, Song S, Wei S, He M, Lin Y, Li Z, Wei M, Yu H, Gu Y, Li S*, Xia N. (2017) Stop codon mutagenesis for homogenous expression of human papillomavirus L1 protein in Escherichia coli., Protein Expr. Purif. 133, 110–120.

18) Li Z, Yan X, Yu H, Wang D, Song S, Li Y, He M, Hong Q, Zheng Q, Zhao Q, Gu Y, Zhang J, Janssen ME, Cardone, G, Olson NH, Baker TS*, Li S*, Xia N. (2016) The C-Terminal Arm of the Human Papillomavirus Major Capsid Protein Is Immunogenic and Involved in Virus-Host Interaction., Structure 24, 874–85.

19) Zhang X, Wang K, Lin Q, et al. A shared N-terminal hydrophobic tail for the formation of nanoparticulates. Nanomedicine, 2016, 11(17): 2289-2303.

20) Gu Y, Tang X, Zhang X, Song C, Zheng M, Wang K, Zhang J, Ng MH, Hew CL, Li S*, Xia N*, Sivaraman J*.Structural basis for theneutralization of hepatitis E virus by a cross-genotype antibody. Cell Res. 2015 May;25(5): 604-20.

21) Li S, Zhang J, Xia N*. Lessons from hepatitis E vaccinedesign.Curr Opin Virol. 2015Apr;11:130-136.

22) Wang D, Li Z, Xiao J, Wang J, Zhang L, Liu Y, Fan F, XinL, Wei M, Kong Z, Yu H, Gu Y, Zhang J, LiS*, Xia N*. Identification of Broad-Genotype HPV L2 Neutralization Site for Pan-HPV Vaccine Development by a Cross-Neutralizing Antibody. PLoS One. 2015 Apr23;10(4):e0123944.

23) Li SW, Zhao Q, Wu T*, Chen S, Zhang J, Xia NS. The development of a recombinant hepatitis E vaccine HEV 239.Hum Vaccin Immunother. 2015;11(4):908-14.

(五)本组优势

我们是一支富有创新性和凝聚力的学术团队,欢迎广大学子报名。

(六)招生要求

生物专业背景优先


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国家传染病诊断试剂与疫苗工程技术研究中心(厦门大学)  地址:中国福建省厦门市翔安区翔安南路厦门大学翔安校区
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