本组主要负责人为陈毅歆教授，现有博后3名，在读博士生7名、在读硕士生10名、技术员5名，是一个充满活力和不断进取的科研小组。本组主要从事流感等人类病毒性传染病和肿瘤等慢性疾病的诊断、治疗和预防领域的基础与应用研究。依托成熟的小鼠、大鼠、禽和兔等单克隆抗体制备技术平台，筛选出各种功能性抗体，辅助疾病关键靶标的基础发现研究，进而指导疫苗、抗病毒药物和诊断试剂的应用转化研究。相关研究成果在Lancet Respiratory Medicine、Science Bulletin、Nature Communication、Sci Transl Med、PNAS、Theranostics、J Virol、J Infect Dis、Clin Microbiol Infect、Emerg Microbes Infect、Virology等SCI刊物上发表50多篇研究论文，其中2017年10月在Science子刊Science Translational Medicine发表的有关乙型流感病毒血凝素头部区广谱中和抗体的研究论文在国际上产生较大影响，流感专家美国科学院院士Peter Palese在Nature撰文评述该研究发现为通用流感疫苗研发带来新的启示；获得美、欧、澳、中等国的发明专利授权18件；研制的诊断试剂盒获得国家药监局颁发的医疗器械注册证16项；禽流感治疗性抗体药物完成临床前研究，获得国家药监局的临床受理1项；研制的鼻喷流感载体新冠疫苗已在我国获批紧急使用; 获得福建省科技奖励2项、厦门市科技奖励3项。目前主要涉及四个研究主题。

1. 流感以及基于流感载体的新冠疫苗研究主题

流感病毒种类繁多且高度变异，长期危害人类健康。我们致力于研究流感病毒的变异规律、寻找其不变的保守靶点，指导通用流感疫苗、广谱抗流感治疗药物和广谱流感诊断试剂的研究，最终实现“一经免疫终身保护”的效果。2005年我们发现禽流感H5N1病毒的首个血凝素（HA）广谱中和抗体及靶标，并首次提出“流感病毒高变异的HA蛋白中存在保守表位”的新概念，引领了以HA为靶标的广谱流感抗体药物和通用流感疫苗的研究热潮，其中的H5 HA广谱单抗因诊断性能优越于2006年获得美国KPCB风险投资公司在中国生物医药领域的首个研究合约。2013年我们研制的跨亚型流感HA广谱中和单抗及靶标再次获得全球制药巨头法国赛诺菲巴斯德公司的通用流感疫苗研究合约，成为该公司在中国疫苗研发领域的第一个合作项目。同时课题组基于流感病毒减毒活疫苗载体DelNS1，初步证实了携带新冠病毒保护性基因的减毒流感病毒载体新冠肺炎疫苗可诱导出流感和新冠的特异性免疫应答，是实现流感和新冠肺炎通用疫苗的可行策略，并初步阐明减毒流感病毒载体新冠肺炎疫苗的保护方式及分子机制，疫苗是国内外最早进入临床试验以及迄今唯一在三期临床试验中验证了安全性和广谱有效性的黏膜免疫新冠疫苗，目前已在我国获批紧急使用。

2. 溶瘤病毒研究主题

溶瘤病毒治疗作为一种新型免疫治疗手段已成为癌症治疗研究的新方向，溶瘤病毒不仅能选择性地杀伤癌细胞，还可以在体内诱发特异性的肿瘤免疫杀伤作用。课题组创新性发现伪狂犬病毒对人肿瘤细胞系具有广谱杀伤活性，在肿瘤模型中展现出了良好的溶瘤疗效，并提交了首个伪狂犬病毒用于肿瘤治疗的相关专利，现已获得中国、日本等多国授权。课题组通过Crisper/Cas9基因编辑技术对病毒基因组进行基因编辑，筛选出安全好、溶瘤活性显著的候选分子，并推动其进行产业化转化，为肿瘤患者开发出新型治疗性药物。

3. 抗体平台研究主题

与被广泛应用的小鼠单抗相比，兔产生的抗体具有独特优势，兔免疫系统可产生更多样的 CDR序列，可获得更多高亲和力和高特异性抗体。对于在小鼠体内无法激起免疫反应的抗原，如小分子、肽段、某些细胞因子及膜蛋白等，兔子体内往往可以达到较好的免疫效果进而获得目标抗体。基于课题组前期构建的兔抗筛选平台，团队主要靶向EB病毒、新冠病毒、肿瘤靶点、免疫靶点等靶标进行抗体筛选工作。在EBV抗体筛选工作中，团队靶向EBV包膜糖蛋白筛选高效中和单抗，结合成熟的体内外功能评价方法和冰冻电镜技术解析关键中和表位，对病毒感染机制进行探究，通过多种展示载体构建表位疫苗以评价不同靶点发展成为EB病毒疫苗的潜力。抗体文库的构建与筛选已成为单抗筛选的重要手段，依托于兔抗筛选平台的研究基础，团队开展了哺乳动物细胞表面展示抗体库技术的研究，利用病毒介导的文库构建，通过哺乳动物细胞表达更接近天然构象的抗体，同时可实现基于流式细胞术分选抗原特异性的细胞。基于病毒介导的哺乳动物细胞展示抗体库是对目前已有的噬菌体展示抗体库的重要补充。

4.肿瘤治疗靶标或肿瘤标志物研究主题

癌症严重危害人类健康，发现新型肿瘤干预靶标，对研制新型肿瘤治疗性抗体药物具有重要意义。另外，肿瘤特异性靶标的相关肿瘤标志物对于肿瘤的早期诊断、治疗预后监测均有重要意义。我们拟通过基于功能抗体的肿瘤靶标正向筛选技术，发现肿瘤新靶标，进而指导肿瘤治疗性抗体药物和肿瘤标志物诊断试剂盒的研发，帮助提升我国癌症患者的生存率。

（二）导师

陈毅歆，邮箱yxchen2008@xmu.edu.cn

（三）正在开展的项目

1. 国家重点研发计划，生物大分子胞内递送系统的研究，在研，主持

2. 国家自然科学基金，基于减毒流感病毒载体的流感和新冠肺炎通用疫苗的免疫保护机制研究，在研，主持

3. 国家自然科学基金，CDCA3调控伪狂犬病毒溶瘤疗效的分子机制研究，在研，主持

（四）近5年来发表的部分文章

1. Chen J, Wang P, Yuan L, Zhang L, Zhang L, Zhao H, Chen C, Wang X, Han J, Chen Y, Jia J, Lu Z, Hong J, Lu Z, Wang Q, Chen R, Qi R, Ma J, Zhou M, Yu H, Zhuang C, Liu X, Han Q, Wang G, Su Y, Yuan Q, Cheng T, Wu T*, Ye X*, Zhang T*, Li C*, Zhang J*, Zhu H*, Chen Y*, Chen H*, Xia N*. A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2. Science Bulletin. 2022 Jul 15;67(13):1372-1387.

2. Zhu F*, Zhuang C, Chu K, Zhang L, Zhao H, Huang S, Su Y, Lin H, Yang C, Jiang H, Zang X, Liu D, Pan H, Hu Y, Liu X, Chen Q, Song Q, Quan J, Huang Z, Zhong G, Chen J, Han J, Sun H, Cui L, Li J, Chen Y*, Zhang T*, Ye X*, Li C*, Wu T*, Zhang J*, Xia NS*. Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials. Lancet Respiratory Medicine. 2022 Aug;10(8):749-760.

3. Li T, Chen J, Zheng Q, Xue W, Zhang L, Rong R, Zhang S, Wang Q, Hong M, Zhang Y, Cui L, He M, Lu Z, Zhang Z, Chi X, Li J, Huang Y, Wang H, Tang J, Ying D, Zhou L, Wang Y, Yu H, Zhang J, Gu Y, Chen Y*, Li S*, Xia N*. Identification of a cross-neutralizing antibody that targets the receptor binding site of H1N1 and H5N1 influenza viruses. Nature Communications. 2022 Sep 2;13(1):5182.

4. Wang G, Zha Z, Huang P, Sun H, Huang Y, He M, Chen T, Lin L, Chen Z, Kong Z, Que Y, Li T, Gu Y, Yu H, Zhang J, Zheng Q, Chen Y*, Li S*, Xia N*. Structures of pseudorabies virus capsids. Nature Communications. 2022 Mar 22;13(1):1533.

5. Zhang X*, Hong J, Zhong L, Wu Q, Zhang S, Zhu Q, Chen H, Wei D, Li R, Zhang W, Zhang X, Wang G, Zhou X, Chen J, Kang Y, Zha Z, Duan X, Huang Y, Sun C, Kong X, Zhou Y, Chen Y, Ye X, Feng Q, Li S, Xiang T, Gao S, Zeng MS, Zheng Q*, Chen Y*, Zeng YX*, Xia N*, Xu M*. Protective anti-gB neutralizing antibodies targeting two vulnerable sites for EBV-cell membrane fusion. Proc Natl Acad Sci U S A. 2022 Aug 9;119(32):e2202371119.

6. Li F, Hong J, Guan C, Chen K, Xie Y, Wu Q, Chen J, Deng B, Shen J, Liu X, Hu R, Zhang Y, Chen Y, Zhu J. Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting. ACS Nano. 2023 Jan 11.

7. Hong J, Wei D, Zhong L, Wu Q, Chen K, Zhang W, Yang Y, Chen J, Xia N, Zhang X*, Chen Y*. Glycoprotein B Antibodies Completely Neutralize EBV Infection of B Cells. Frontiers in Immunology. 2022 May 27;13:920467.

8. Hong J, Zhong L, Zheng Q, Wu Q, Zha Z, Wei D, Chen H, Zhang W, Zhang S, Huang Y, Chen K, Chen J, Li S, Zeng MS, Zeng YX, Xia N, Zhang X*, Xu M*, Chen Y*. A Neutralizing Antibody Targeting gH Provides Potent Protection against EBV Challenge In Vivo. Journal of Virology. 2022 Apr 27;96(8): e0007522.

9. Wang X*, Yin X, Zhang B, Liu C, Lin Y, Huang X, Li Y, Shen C, Zheng W, Fu G, Chen J, Wen Y, Zhang W, Pan BS, Fang M, Zheng Z, Zhang Z, Yuan Q, Fu G, Li S, Zhang J, Chen Y*, Xia N*, Zhao Q*. A prophylactic effect of aluminium-based adjuvants against respiratory viruses via priming local innate immunity. Emerging Microbes & Infections. 2022 Dec;11(1):914-925.

10. Zhang L, Chen J, Shen C, Wang G, Lu Z, Zeng D, Gao Y, Chen H, Xia N, Chen Y*. Vaccination with Deglycosylated Modified Hemagglutinin Broadly Protects against Influenza Virus Infection in Mice and Ferrets. Vaccines. 2022 Aug 11;10(8):1304.

11. Zeng D, Xin J, Yang K, Guo S, Wang Q, Gao Y, Chen H, Ge J, Lu Z, Zhang L, Chen J, Chen Y*, Xia N. A Hemagglutinin Stem Vaccine Designed Rationally by AlphaFold2 Confers Broad Protection against Influenza B Infection. Viruses. 2022 Jun 14;14(6):1305.

12. Chen Y, Shen C*, Chen J, Chen J, Chen F, Zhang L, Liu X, Chen S, Xue S, Liu Y, Tang J, Yuan Q, Chen Y*, Luo W*, Xia N. Development of functional antibodies against influenza B virus by activation-induced cytidine deaminase in hybridoma cells. Virologica Sinica. 2022 Aug;37(4):619-622.

13. Wang G, Chen R, Huang P, Hong J, Cao J, Wu Q, Zheng W, Lin L, Han Q, Chen Y*, Xia N. Adefovir dipivoxil efficiently inhibits the proliferation of pseudorabies virus in vitro and in vivo. Antiviral Research. 2021 Feb;186: 105014.

14. Hong J, Wei D, Wu Q, Zhong L, Chen K, Huang Y, Zhang W, Chen J, Xia N, Zhang X, Chen Y*. Antibody Generation and Immunogenicity Analysis of EBV gp42 N-Terminal Region. Viruses. 2021 Nov 28;13(12):2380.

1. Hong, J., Wu, Q., Wang, Q., Chen, J., Wang, X., Wang Y., Chen, Y., Xia, N. Rabbit Monoclonal Antibody Specifically Recognizing a Linear Epitope in the RBD of SARS-CoV-2 Spike Protein. Vaccines (Basel). 2021 Aug; 9(8): 829.

2. Hong, J., Wei, D., Wu, Q., Zhong, L., Chen, K., Huang, Y., Zhang, W., Chen, J., Xia, N., Zhang, X., Chen, Y. Antibody Generation and Immunogenicity Analysis of EBV gp42 N-Terminal Region. Viruses. 2021 Dec; 13(12): 2380.

3. Wang, G., Chen, R., Huang, P., Hong, J., Cao, J., Wu, Q., Lin, L., Han, Q., Chen, Y., Xia, N. Adefovir dipivoxil efficiently inhibits the proliferation of pseudorabies virus in vitro and in vivo. Antiviral research. 2021 Feb;186:105014.

4. Wang, G., Huang, P., Hong, J., Fu, R., Wu, Q., Chen, R., Lin, L., Han, Q., Chen, H., Chen, Y., Xia, N. Establishment of a rapid ELISPOT assay for influenza virus titration and neutralizing antibody detection. Journal of Medical Virology. 2020 Jul 4. 2020;1–10.

5. Shen C, Zhang M, Chen Y, Zhang L, Wang G, Chen J, Chen S, Li Z, Wei F, Chen J, Yang K, Guo S, Wang Y, Zheng Q, Yu H, Luo W, Zhang J, Chen H, Chen Y*, Xia N. An IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency. Theranostics. 2019 Jan 1;9(1):210-231.

6. Chen J, Yang K, Zhang M*, Shen C, Chen J, Wang G, Huang S, Zhang M, Xiong H, Chen H, Chen Y*, Xia N. Rapid identification of imported influenza viruses at Xiamen International Airport via an active surveillance program. Clinical Microbiology and Infection, 2018 Mar;24(3):289-294.

7. Woo PCY #, Lau SKP #, Chen Y #, Wong EYM, Chan KH, Chen H, Zhang L, Xia N, Yuen KY. Rapid detection of MERS coronavirus-like viruses in bats: potential for tracking MERS coronavirus transmission and animal origin. Emerging Microbes & Infections. 2018 Mar 7;7(1):18.

8. Lin Q #, Li T #, Chen Y #, Lau SY, Wei M, Zhang Y, Zhang Z, Yao Q, Li J, Li Z, Wang D, Zheng Q, Yu H, Gu Y, Zhang J, Chen H, Li S, Xia N. Structural Basis for the Broad, Antibody-Mediated Neutralization of H5N1 Influenza Virus. Journal of Virology. 2018 Aug 16;92(17).

9. Shen C, Chen J, Li R, Zhang M, Wang G, Stegalkina S, Zhang L, Chen J, Cao J, Bi X, Anderson SF, Alefantis T, Zhang M, Cai X, Yang K, Zheng Q, Fang M, Yu H, Luo W, Zheng Z, Yuan Q, Zhang J, Wai-Kuo Shih J, Kleanthous H, Chen H, Chen Y*, Xia N*. A multimechanistic antibody targeting the receptor binding site potently cross-protects against influenza B viruses. Science Translational Medicine. 2017 Oct 18;9(412).

10. Chen Y, Chan KH, Hong C, Kang Y, Ge S, Chen H, Wong EY, Joseph S, Patteril NG, Wernery U, Xia N, Lau SK, Woo PC. A highly specific rapid antigen detection assay for on-site diagnosis of MERS. Journal of Infection. 2016 Jul;73(1):82-4.

11. Zhang P #, Chen Y #, Zeng Y #, Shen C, Li R, Guo Z, Li S, Zheng Q, Chu C, Wang Z, Zheng Z, Tian R, Ge S, Zhang X, Xia NS, Liu G, Chen X. Virus-mimetic nanovesicles as a versatile antigen-delivery system. Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):E6129-38.

12. Chen Y, Chan KH, Kang Y, Chen H, Luk HK, Poon RW, Chan JF, Yuen KY, Xia N, Lau SK, Woo PC. A sensitive and specific antigen detection assay for Middle East respiratory syndrome coronavirus. Emerging Microbes & Infections. 2015 Apr;4(4):e26.

13. Gui X, Li R, Zhang X, Shen C, Yu H, Guo X, Kang Y, Chen J, Chen H, Chen Y*, Xia N*. An important amino acid in nucleoprotein contributes to influenza A virus replication by interacting with polymerase PB2. Virology, 2014, 464-465:11-20.

14.  Gui X, Ge P, Wang X, Yang K, Yu H, Zhao Q, Chen Y*, Xia N*. Identification of a highly conserved and surface exposed B-cell epitope on the nucleoprotein of influenza A virus. Journal of Medical Virology, 2014, 86:995-1002.

15. Chen Y #, Li C #, He D, Cheng T, Ge S, Shih JW, Zhao Q, Chen P-J, Zhang J, Xia N. Antigenic analysis of divergent genotypes human Enterovirus 71 viruses by a panel of neutralizing monoclonal antibodies: Current genotyping of EV71 does not reflect their antigenicity. Vaccine, 2013, 31:425-30.

16. Wu WL, Lau SY, Chen Y, Wang G, Mok BW, Wen X, Wang P, Song W, Lin T, Chan KH, Yuen KY, Chen H. The 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: Implications for the prevalence of oseltamivir resistant variant viruses. Antiviral Research, 2012, 93:144-153.

17. Chen Y #, Zheng Q #, Yang K, Zen F, Lau S-Y, Wu WL, Huang S, Zhang J, Chen H, Xia N. Serological survey of antibodies to influenza A viruses on a group of people without a history of influenza vaccination. Clinical Microbiology and Infection, 2011, 17:1347-1349.

18. Zheng Q, Xia L, Wu WL, Zheng Z, Huo Y, Wu J, Liu Y, Yu H, Chen Y, Lau SY, Chen H, Luo W, Xia N. Properties and therapeutic efficacy of broadly reactive chimeric and humanized H5-specific monoclonal antibodies against H5N1 influenza viruses. Antimicrobial Agents and Chemotherapy, 2011, 55:1349-1357.

19. Chen Y, Xu F, Gui X, Yang K, Wu X, Zheng Q, Ge S, Yuan Q, Yeo AET, Zhang J, Guan Y, Chen H, Xia N. A rapid test for the detection of influenza A virus including pandemic influenza A/H1N1 2009. Journal of Virological Methods, 2009, 167:100-102.

20. Chen Y #, Qin K #, Wu WL, Li G, Zhang J, Du H, Ng MH, Shih JWK, Peiris JSM, Guan Y, Chen H, and Xia N. Broad Cross-Protection against H5N1 Avian Influenza Virus Infection by Means of Monoclonal Antibodies that Map to Conserved Viral Epitopes. Journal of Infectious Diseases, 2009, 199:49-58.

21. WL Wu #, Chen Y #, Wang P, Song W, Lau SY, Rayner JM, Smith GJD, Webster RG, Peiris JSM, Lin T, Xia N, Guan Y and Chen H. Antigenic profile of avian H5N1 viruses in Asia from 2002 to 2007. Journal of Virology, 2008, 82:1798-1807.

22. Chen Y, F Xu, X Fan, H Luo, S Ge, Q Zheng, N Xia, H Chen, Y Guan, and J Zhang. Evaluation of a rapid test for detection of H5N1 avian influenza virus. Journal of Virological Methods, 2008, 154:213-215.

（五）招生要求

招收专业：生物学、生物化学与分子生物学、细胞生物学、微生物学、生物制品学、转化医学、公共卫生与预防医学、临床医学、公共卫生硕士等专业。

科研除了要具备探索精神，还需要积极乐观的心态，欢迎志同道合的广大学子报名单克隆抗体组。