研究系列

倪凌

清华大学医学院副研究员

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探究人体免疫学以及囊膜病毒感染和疫苗新机制

倪凌,副研究员。2005年博士毕业于中科院微生物研究所;2006年在美国达拉斯贝勒免疫研究所开展博士后研究工作;2014年8月回国加入清华大学医学院董晨教授课题组。

囊膜病毒感染机制及靶向树突状细胞的疫苗设计

倪凌一直从事于囊膜病毒的研究,包括SARS-CoV,HIV-1,RSV,流感和SARS-CoV-2,对囊膜病毒入侵宿主细胞以及其后宿主产生的免疫应答积攒丰富的经验和知识。在前期工作中利用SARS-CoV S蛋白, RSV F蛋白和HIV-1 gp41的七肽重复序列设计了蛋白多肽抑制剂,能有效地抑制病毒入侵宿主细胞;在流感的研究中,设计了靶向树突状细胞的流感疫苗,有效地引起宿主针对病毒特异性的抗体和细胞免疫反应;最近,对COVID-19康复轻症患者的免疫学特征进行了分析, 首次在国内外发现了康复者体内的T细胞和抗体参与机体保护,并发现重症患者在急性期就产生了SARS-CoV-2特异性的体液反应,包括中和抗体,但SARS-CoV-2特异性细胞反应严重受损。

她设计了靶向树突状细胞的流感疫苗,能有效地引起宿主针对病毒特异性的抗体和细胞免疫反应,并发现靶向树突状细胞不同受体分子会引起不同类型的T细胞反应;于2020和2021年对新冠肺炎患者的体液和细胞免疫反应进行解析并参与中国第一个新冠病毒mRNA疫苗临床试验。目前正在开展新冠病毒灭活疫苗引起的免疫反应持久性的研究。

1.Ling Ni#, Meng-Li Cheng#, Yu Feng#, Hui Zhao#, Jingyuan Liu, Fang Ye, Qing Ye, Gengzhen Zhu, Xiaoli Li, Pengzhi Wang, Jing Shao, Yong-Qiang Deng, Peng Wei, Fang Chen, Cheng-Feng Qin, Guoqing Wang, Fan Li*, Hui Zeng*, Chen Dong*. Impaired cellular immunity to SARS-CoV-2 in severe COVID-19 patients. Frontiers in immunology. 2020.

2.Ling Ni#, Fang Ye#, Meng-Li Cheng#, Yu Feng, Yong-Qiang Deng, Hui Zhao, Peng Wei, Jiwan Ge, Mengting Gou, Xiaoli Li, Lin Sun, Tianshu Cao, Pengzhi Wang, Chao Zhou, Rongrong Zhang, Peng Liang, Han Guo, Xinquan Wang, Cheng-Feng*, Qin Fang Chen*, Chen Dong*. Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2. Immunity. 2020, 52, 971-977.

3.Ling Ni, Yu Feng, Chen Dong*. The advancement of immunotherapy in HCC. Hepatoma Research. 2020. 6:25.

4.Dongli Cai, Jiaming Li, Dingfeng Liu, Shanjuan Hong, Qin Qiao, Qinli Sun, Pingping Li, Nanan Lyu, Tiantian Sun, Shan Xie, Li Guo, Ling Ni*, Liping Jin*, Chen Dong*. Tumor-expressed B7-H3 mediates the inhibition of antitumorT-cell functions in ovarian cancer insensitive to PD-1blockade therapy. Cellular&molecular immunology. 2019. 17(3):227-236.

5.Shanjuan Hong, Qing Yuan, Haizhui Xia, Genzhen Zhu, Yu Feng, Qiang Wang, Zhiyin Zhang, Wei He, Jian Lu*, Chen Dong*, Ling Ni*. Analysis of VISTA expression and function in renal cell carcinoma highlights VISTA as a potential target for immunotherapy. Protein&cell. 2019.10(11):840-845.

6.Shan Xie, Jia Huang, Qin Qiao, Wenjuan Zang, Shanjuan Hong, Haidong Tan, Chen Dong, Zhiying Yang*, Ling Ni*. Expression of inhibitory B7 family molecule VISTA in human colorectal carcinoma tumors. Cancer Immunology, Immunotherapy. 2018, 67:1685-1694

7.Ling Ni* and Jian Lu*. Inferferon gamma in cancer immunotherapy. Cancer medicine. 2018; 7(9): 4509-4516

8.Ling Ni* and Chen Dong*. Roles of Myeloid and Lymphoid Cells in the Pathogenesis of Chronic Obstructive Pulmonary Disease. Frontiers in immunology. 2018; 9: 1-12.

9.Ling Ni*. Comparison of PD-L1 and B7-H3 in cancer immunotherapy. Journal of immunology and immunotherapy. 2017; 1(1): 1-3

10.Ling Ni*. Non-redundant roles of new immune checkpoints in cancer evasion. Immunotherapy. 2017; 3(3):144-145

11.Ling Ni*, Chen Dong. New B7 family checkpoints in human cancers. Mol Cancer Ther. 2017; 16 (7): 1203-1211

12.Ling Ni*, Chen Dong*. New checkpoints in cancer immunotherapy. Immunological reviews. 2017; 276(1): 52-65

13.Ling Ni, Ingrid Gayet, Sandra Zurawski, Dorothee Duluc, Anne-Laure Flamar, Xiao-Hua Li, Amy O’Bar, Anna Karolina Palucka, Gerard Zurawski, Jacques Banchereau, and SangKon Oh*. Concomitant activation and antigen uptake via human Dectin-1 results in potent antigen-specific CD8+ T cell responses. Journal of immunology. 2010, 185(6): 3504-13.

14.Ling Ni, Linqing Zhao, Jieqing Zhu, Zhibo Jin, Po Tien* and George F. Gao*. Design and characterization of human respiratory syncytial virus entry inhibitors. Antiviral Therapy, 2005 (7): 833-40

15.Ling Ni, Jieqing Zhu, Junjie Zhang, Meng Yan, George F. Gao*, Po Tien*. Design of recombinant protein-based SARS-CoV entry inhibitors targeting the heptad-repeat regions of the spike protein S2 domain. Biochemical and Biophysical research communications, 2005 (330): 39-45.

16.Ling Ni, Linqing Zhao, George F. Gao, Yuan Qian and Po Tien*. The antibodies directed against N-terminal heptad-repeat peptide of hRSV fusion protein and its analog-5-Helix inhibit virus infection in vitro. Biochemical and Biophysical research communications, 2005 (331): 1358-1364.

17.Ling Ni, George F. Gao*,Po Tien*. Rational design of highly potent HIV-1 fusion inhibitory proteins: implication for developing antiviral therapeutics. Biochemical and Biophysical research communications, 2005(332): 831-836.

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