抗体治疗组

   

(一)本组简介

本研究小组现有8位成员(含博士、研究生、技术员)。旨在建立完善利用细胞模型和重组抗原等进行抗病毒的单抗筛选,包括针对HIV-1Env包膜蛋白平台、Gag蛋白平台、人受体及辅助受体的功能抗体。自主发展了适用于HIV-1EnvGag等抗原的原核、真核表达系统,并借助结构生物学和细胞模型开展HIV-1免疫原设计工作。在HIV-1诊断试剂盒和试剂标准品研发方面,长期与万泰保持紧密合作关系。本小组目前已获得多种HIV-1中和单抗、HIV-1GagEnv高亲和力单克隆抗体、针对人HIV-1受体的高亲和力单克隆抗体以及基于HIV-1Gag颗粒结构的嵌合抗原分子,将应用生物传感器、分析超离、微量热等X射线晶体衍射和冷冻电镜(Cryo-EM)等方法研究抗原抗体相互作用和特征结构。并利用真病毒、假病毒细胞模型以及免疫学实验鉴定抗体对应的功能性表位,为揭露HIV-1感染人体机制和阻止HIV-1感染复制的抗体治疗策略提供理论基础。

除基于HIV-1开展相关研究以外,新冠疫情期间,本研究小组开展了SARS COV-2抗体筛选工作,并已获得多株具有良好中和效果和交叉中和效果的单克隆抗体,并正开展抗原抗体结构研究。

主持4项国家自然科学基金项目、1项国家科技重大专项子课题,1项福建省科技重大项目,获得专利授权4项。

(二)导师

顾颖

(三)正在开展的项目

  1. 靶向CD4受体的人类免疫缺陷病毒中和抗体的作用机制和表位结构研究

  2. 基于结构的人免疫缺陷病毒衣壳组装机理及功能表位的研究

  3. HIV免疫原设计、中和单抗筛选及其结构解析

  4. SARS COV-2中和抗体筛选及抗原抗体结构解析

(四)近5年来发表的部分文章

1. Shen CH, DeKosky BJ, Guo Y, Xu K, Gu Y, Kilam D, Ko SH, Kong R, Liu K, Louder MK, Ou L, Zhang B, Chao CW, Corcoran MM, Feng E, Huang J, Normandin E, O'Dell S, Ransier A, Rawi R, et al. VRC34-Antibody Lineage Development Reveals How a Required Rare Mutation Shapes the Maturation of a Broad HIV-Neutralizing Lineage. Cell Host Microbe. 2020 Apr 8;27(4):531-543.e6. doi: 10.1016/j.chom.2020.01.027. Epub 2020 Mar 3.

2. Zheng Q, Jiang J, He M, Zheng Z, Yu H, Li T, Xue W, Tang Z, Ying D, Li Z, Song S, Liu X, Wang K, Zhang Z, Wang D, Wang Y, Yan X, Zhao Q, Zhang J, Gu Y, Li S, Xia N. Viral neutralization by antibody-imposed physical disruption. Proc Natl Acad Sci U S A. 2019 Dec 9;116(52):26933–40. doi: 10.1073/pnas.1916028116. Epub ahead of print.

3. Liu X, Chen J, Wang Z, Wang D, He M, Qian C, Song S, Chi X, Kong Z, Zheng Q, Wang Y, Yu H, Zhao Q, Zhang J, Li S, Gu Y, Xia N. Neutralization sites of human papillomavirus-6 relate to virus attachment and entry phase in viral infection. Emerg Microbes Infect. 2019;8(1):1721-1733.

4. Zhang Z, Wei X, Lin Y, Huang F, Shao J, Qi J, Deng T, Li Z, Gao S, Li S, Yu H, Zhao Q, Li S, Gu Y, Xia N. HIV-1 Membrane-Proximal External Region Fused to Diphtheria Toxin Domain-A Elicits 4E10-Like Antibodies in Mice. Immunol Lett. 2019 Sep;213:30-38. doi: 10.1016/j.imlet.2019.07.004. Epub 2019 Jul 26.

5.Kong R, Duan H, Sheng Z, Xu K, Acharya P, Chen X, Cheng C, Dingens AS, Gorman J, Sastry M, Shen CH, Zhang B, Zhou T, Chuang GY, Chao CW, Gu Y, Jafari AJ, Louder MK, O'Dell S, Rowshan AP, Viox EG, Wang Y, Choi CW, Corcoran MM, Corrigan AR, Dandey VP, Eng ET,et al. Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. Cell. 2019 Jul 25;178(3):567-584.e19.

6.Li T, Zhang Z, Zhang Z, Qiao J, Rong R, Zhang Y, Yao Q, Li Z, Shen H, Huang F, Xue W, Gao S, Li S, Zheng Q, Yu H, Zhang J, Gu Y*, Li S*, Xia N. Characterization of native-like HIV-1 gp140 glycoprotein expressed in insect cells. Vaccine. 2019 Feb 5. pii: S0264-410X(19)30124-0. doi: 10.1016.

7. Zhang Z, Zhang F, Bai S, Qiao J, Shen H, Huang F, Gao S, Li S, Gu Y*, Xia N. Characterization and epitope mapping of a panel of monoclonal antibody against HIV-1 matrix protein. Biotechnol Appl Biochem. 2018 Apr 17. doi: 10.1002/bab.1662.

8. Zhang Z, Wang L, Bai S, Qiao J, Shen H, Huang F, Gao S, Li S, Li S, Gu Y*, Xia N. Expression, Purification and Characterization of HIV-1 Capsid Precursor Protein p41. Protein J. 2018 Mar 5. doi: 10.1007/s10930-018-9763-0.

9. 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.

10. 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

11. Gu, Ying#; Wei, Minxi# ; Wang, Daning; Li, Zhihai; Xie, Minghui; Pan, Huirong; Wu, Ting; Zhang, Jun; Li, Shaowei*; Xia, Ningshao*, Characterization of an Escherichia coil-derived human papillomavirus type 16 and 18 bivalent vaccine, VACCINE, 2017.8.16, 35(35): 4637~4645.

12. Zhang Z, Li S, Gu Y*, Xia N. Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies. Int J Mol Sci. 2016 Nov 18;17(11).

13. Zhang Z, Zhang F, Yang C, Qi J, Gao S, Li S, Gu Y*, Xia N. HIV-1 Capsid as a Target for Antiviral Therapy. J AIDS Clin Res 7:536. 2016 Jan. doi:10.4172/2155-6113.1000536

14.Yuan R, Qi J, Zhang Z, Li S, Gu Y*, Xia N. Anti-CD4: An Alternative Way to Inhibit HIV Infection. J HIV & Retro Virus. 2016 Jan.

15. Hou W, Fang C, Liu J, Yu H, Gu Y* et al. Molecular insights into the inhibition of HIV-1 infection using a CD4 domain-1-specific monoclonal antibody. Antiviral Res. 2015 Aug; 122:101-11.

16.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 the neutralization of hepatitis E virus by a cross-genotype antibody. Cell Res. 2015 May;25(5):604-20.

17. Wang D, Li Z, Xiao J, Wang J, Zhang L, Liu Y, Fan F, Xin L, Wei M, Kong Z, Yu H, Gu Y, Zhang J, Li S, Xia N. Identification of Broad-Genotype HPV L2 Neutralization Site for Pan-HPV Vaccine Development by a Cross-Neutralizing Antibody. PLoS One. 2015 Apr 23;10(4):e0123944.

(五)招生要求

1.专业:生物学或医学专业优先

2.成绩排名:本专业排名前四十以上

3.国家四六级英语考试425分及以上

4.专业基础知识扎实,实验动手能力较强,具有探索精神和一定的写作能力,大学期间有科研经验者优先

5.做事认真,负责,具有良好的团队合作精神


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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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