中和抗体在新型冠状病毒肺炎治疗中的重要意义: 进展与展望

doi:10.5246/jcps.2021.02.008

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (2): 87-106.DOI: 10.5246/jcps.2021.02.008

• 【综述】 • 下一篇

中和抗体在新型冠状病毒肺炎治疗中的重要意义: 进展与展望

周泽奇¹^,²^,^*(), 王祥斌³^,^*(), 张喜庆¹^,², 张园¹^,², 付彦凯¹^,², 王志贤¹^,², 粟艳¹^,², 王贺¹^,², 肖盟⁴^,⁵, 刘昌孝⁶^,^*()

1. "侵袭性真菌疾病机制研究与精准诊断重点实验室"北京市重点实验室丹娜生物分中心, 天津 300467
2. 天津市侵袭性真菌病精准诊断技术企业重点实验室, 天津 300467
3. 北京安泰至远科技有限公司, 北京 102206
4. 中国医学科学院北京协和医院临床微生物实验室, 北京 100730
5. 北京市侵袭性真菌病机制研究与精确诊断重点实验室(bz0447), 北京 100730
6. 释药技术与药代动力学国家重点实验室天津药物研究院, 天津 300462

收稿日期:2020-12-10 修回日期:2020-12-24 接受日期:2021-01-27 出版日期:2021-02-28 发布日期:2021-02-28
通讯作者: 周泽奇, 王祥斌, 刘昌孝
作者简介:
+ Tel.: +86-13602196602, E-mail: liuchangxiao@163.com
+ E-mail: zeqizhou8888@dynamiker.com
+ E-mail: xb.wang@abfound.com
基金资助:
China Postdoctoral Science Foundation (Grant No. 2020T1300011ZX); National Science and Technology Major Project (Grant No. 2018ZX10712001); Key Research and Development Projects of Tianjin Science and Technology Committee (Grant No. 17YFZCSY00660).

Significance of neutralizing antibodies in COVID-19 therapy: progress and prospect

Zeqi Zhou¹^,²^,^*(), Xiangbin Wang³^,^*(), Xiqing Zhang¹^,², Yuan Zhang¹^,², Yankai Fu¹^,², Zhixian Wang¹^,², Yan Su¹^,², He Wang¹^,², Meng Xiao⁴^,⁵, Changxiao Liu⁶^,^*()

1 Dynamiker Sub-Center of Beijing Key Laboratory for?Mechanisms Research and Precision Diagnosis of Invasive?Fungal Disease, Tianjin 300467, China
2 Tianjin?Enterprise Key Laboratory for?Precision Diagnosis Technology of?Invasive Fungal Diseases, Tianjin 300467, China
3 Beijing Antai Zhiyuan Technology Co., Ltd., Beijing 102206, China
4 Clinical Laboratory, Peking Union Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
5 Beijing Key Laboratory Beijing for Mechanism Study and Precision Diagnosis of Invasive Fungal Diseases (bz0447), Beijing 100730, China
6 State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300462, China

Received:2020-12-10 Revised:2020-12-24 Accepted:2021-01-27 Online:2021-02-28 Published:2021-02-28
Contact: Zeqi Zhou, Xiangbin Wang, Changxiao Liu

About author:

Changxiao Liu, pharmacologist, pharmacokinetic expert, Academician of Chinese Academy of Engineering, researcher, doctoral supervisor. He graduated from Beijing Medical College in 1965 with a bachelor's degree. He is currently the dean of School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, director of State Key Laboratory of Drug Release Technology and Pharmacodynamics of Tianjin Pharmaceutical Research Institute, and has served as the chairman of Drug Metabolism Professional Committee of Chinese Pharmacological Society. One of the pioneers and leaders of pharmacokinetics in China.

摘要/Abstract

摘要：

SARS-CoV-2感染是对全世界人类生命和健康的一大严重威胁, 新型冠状病毒肺炎是由SARS-CoV-2感染引起的全球流行病。SARS-CoV-2病毒具有高度的传染性、诡异性和多变性。因此, 新型冠状病毒肺炎的治疗是紧迫且有针对性的。然而, 疫苗和目前使用的药物一般不具有上述特点。虽然新型冠状病毒肺炎的恢复期血浆在危重患者的急诊治疗中已显示出临床应用价值, 但仍具有很大的局限性。全人源重组多价中和纳米抗体可能满足新型冠状病毒肺炎治疗的不足。基因工程技术已被应用于开发特异性中和抗体(nAB)药物, 用于治疗世界范围内的新型冠状病毒肺炎。一些候选的nAB药物已经进入临床试验, 并且可以很快用于新型冠状病毒肺炎的治疗。在本综述中, 我们从以下五个方面分析和研究nABs治疗新型冠状病毒肺炎的进展和前景: 1) SARS-CoV-2感染的生物学和临床特点; 2) 新型冠状病毒肺炎康复者血浆治疗的可行性; 3) 开发nAB药物的技术路线; 4) 开发全球新型冠状病毒中和抗体的现状; 5) 困难和临床应用前景。

关键词: SARS-CoV-2, 中和抗体(nAB), 新型冠状病毒肺炎

Abstract:

SARS-CoV-2 infection is a serious threat to human life and health all over the world, and COVID-19 is a global epidemic caused by SARS-CoV-2 infection. SARS-CoV-2 is highly infectious, strange and variable. Therefore, the treatment of COVID-19 must be urgent and targeted. However, vaccines and currently used drugs generally do not have the above-mentioned characteristics. Although convalescent plasma of COVID-19 has shown a clinical application value in the emergency treatment of critical patients, it shows great limitations. All human recombinant multivalent neutralizing nano-antibodies may meet the deficiency of COVID-19 therapy. Gene engineering technologies have been used to develop specific neutralizing antibody (nAB) drugs for the treatment of COVID-19 worldwide. Some of the candidate nAB drugs have been entered the clinical trials and can be used for the therapy of COVID-19 shortly. In the present review, we studied and analyzed nABs for the treatment of COVID-19 and the progress and prospect from the following five aspects: 1) The biological and clinical characteristics of SARS-CoV-2 infection; 2) The feasibility of plasma therapy for convalescents with COVID-19; 3) The technical routes of developing nAb drugs; 4) The current status of developing global COVID-19 antibodies; 5) The difficulties and clinical use.

Key words: SARS-CoV-2, Neutralizing antibody (nAB), COVID-19

Supporting:

周泽奇, 王祥斌, 张喜庆, 张园, 付彦凯, 王志贤, 粟艳, 王贺, 肖盟, 刘昌孝. 中和抗体在新型冠状病毒肺炎治疗中的重要意义: 进展与展望[J]. 中国药学(英文版), 2021, 30(2): 87-106.

Zeqi Zhou, Xiangbin Wang, Xiqing Zhang, Yuan Zhang, Yankai Fu, Zhixian Wang, Yan Su, He Wang, Meng Xiao, Changxiao Liu. Significance of neutralizing antibodies in COVID-19 therapy: progress and prospect[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(2): 87-106.

图/表 5

Figure 1. The structure and immune response of SARS-CoV-2 neutralization.

Figure 2. Discovery process of fully human anti-SARS-CoV-2 nABs from PBMCs of COVID-19 convalescent patients.

Figure 3. Discovery process of anti-SARS-CoV-2 neutralizing nanobodies.

Table 1. Clinical status of SARS-CoV-2 neutralizing antibodies.

Figure 4. ADE effect of SARS-CoV-2.

参考文献 54

[1]	Cao, Y.L.; Su, B.; Guo, X.H.; Sun, W.J.; Deng, Y.Q.; Bao, L.L.; Zhu, Q.Y.; Zhang, X.; Zheng, Y.H.; Geng, C.Y.; Chai, X.R.; He, R.S.; Li, X.F.; Lv, Q.; Zhu, H.; Deng, W.; Xu, Y.F.; Wang, Y.J.; Xie, X.S. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell. 2020, 182, 73–84.e16.
[2]	Zhou, Z.; Wang, X.; Fu, Y.; Zhang, X.; Liu, C. Letter to the editor: Neutralizing antibodies for the treatment of COVID-19. Acta Pharm. Sin. B. 2021, 11, 304–307.
[3]	Davies, N.G.; Barnard, R.C.; Jarvis, C.I.; Kucharski, A.J.; Munday, J.; Pearson, C.A.B. Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England. medRxiv. [Preprint.]. December. 24, 2020 [accessed 2020 December 30]. Available from: https://www.medrxiv.org/content/10.1101/2020.12.24. 20248822v1.
[4]	Zhu, N.; Zhang, D.Y.; Wang, W.L.; Li, X.W.; Yang, B.; Song, J.D.; Zhao, X.; Huang, B.Y.; Shi, W.F.; Lu, R.J.; Niu, P.H.; Zhan, F.X.; Ma, X.J.; Wang, D.Y.; Xu, W.B.; Wu, G.Z.; Gao, G.F.; Tan, W.J. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med. 2020, 382, 727–733.
[5]	Forster, P.; Forster, L.; Renfrew, C.; Forster, M. Phylogenetic network analysis of SARS-CoV-2 genomes. Proc. Natl. Acad. Sci. USA. 2020, 117, 9241–9243.
[6]	Liu, X.; Wang, X.J. Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines. J. Genet. Genom. 2020, 47, 119–121.
[7]	Zou, X.; Chen, K.; Zou, J.W.; Han, P.Y.; Hao, J.; Han, Z.G. Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 2020, 14, 185–192.
[8]	Wang, C.Y.; Li, W.T.; Drabek, D.; Okba, N.M.A.; van Haperen, R.; Osterhaus, A.D.M.E.; van Kuppeveld, F.J.M.; Haagmans, B.L.; Grosveld, F.; Bosch, B.J. A human monoclonal antibody blocking SARS-CoV-2 infection. Nat. Commun. 2020, 11, 2251.
[9]	Jia, Y.; Shen, G.; Nguyen, S.; Zhang, Y.; Huang, K.S.; Ho, H.Y.; Hor, W.S.; Yang, C.H.; Bruning, John B. Li, C.D. Wang, W.L. Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity. bioRxiv. [Preprint.]. April 9, 2020 [accessed 2020 May 5] Available from: https://www.biorxiv.org/content/10.1101/2020.04.09.034942v2.
[10]	Shen, C.G.; Wang, Z.Q.; Zhao, F.; Yang, Y.; Li, J.X.; Yuan, J.; Wang, F.X.; Li, D.L.; Yang, M.H.; Xing, L.; Wei, J.L.; Xiao, H.X.; Yang, Y.; Qu, J.X.; Qing, L.; Chen, L.; Xu, Z.X.; Peng, L.; Li, Y.J.; Zheng, H.X.; Chen, F.; Huang, K.; Jiang, Y.J.; Liu, D.J.; Zhang, Z.; Liu, Y.X.; Liu, L. Treatment of 5 critically ill patients with COVID-19 with convalescent plasma. JAMA. 2020, 323, 1582–1589.
[11]	General Office of the National Health Commission of PRC [Internet]. The Novel Coronavirus Pneumonia Convalescent Plasma Treatment Plan (Trial Version 2). [cited 2020 Feb 5]. Available from: http://www.gov.cn/zhengce/zhengceku/2020-03/05/content 5487145.htm.
[12]	Ravi, N.; Cortade, D.L.; Ng, E.; Wang, S.X. Diagnostics for SARS-CoV-2 detection: a comprehensive review of the FDA-EUA COVID-19 testing landscape. Biosens. Bioelectron. 2020, 165, 112454.
[13]	Panda, S.; Ravindran, B. Isolation of human PBMCs. Bio-protocol. 2013, 3. DOI:10.21769/bioprotoc.323.
[14]	Gautam, A.; Donohue, D.; Hoke, A.; Miller, S.A.; Srinivasan, S.; Sowe, B.; Detwiler, L.; Lynch, J.; Levangie, M.; Hammamieh, R.; Jett, M. Investigating gene expression profiles of whole blood and peripheral blood mononuclear cells using multiple collection and processing methods. PLoS One. 2019, 14, e0225137.
[15]	Shui, X.; Huang, J.; Li, Y.H.; Xie, P.L.; Li, G.C. Construction and selection of human Fab antibody phage display library of liver cancer. Hybridoma(Larchmt). 2009, 28, 341–347.
[16]	Mulangu, S.; Dodd, L.E.; Davey, R.T.; Tshiani Mbaya, O.; Proschan, M.; Mukadi, D.; Lusakibanza Manzo, M.; Nzolo, D.; Tshomba Oloma, A.; Ibanda, A.; Ali, R.; Coulibaly, S.; Levine, A.C.; Grais, R.; Diaz, J.; Lane, H.C.; Muyembe-Tamfum, J.J.; Group, P.W.; Sivahera, B.; Camara, M.; Kojan, R.; Walker, R.; Dighero-Kemp, B.; Cao, H.; Mukumbayi, P.; Mbala-Kingebeni, P.; Ahuka, S.; Albert, S.; Bonnett, T.; Crozier, I.; Duvenhage, M.; Proffitt, C.; Teitelbaum, M.; Moench, T.; Aboulhab, J.; Barrett, K.; Cahill, K.; Cone, K.; Eckes, R.; Hensley, L.; Herpin, B.; Higgs, E.; Ledgerwood, J.; Pierson, J.; Smolskis, M.; Sow, Y.; Tierney, J.; Sivapalasingam, S.; Holman, W.; Gettinger, N.; Vallée, D.; Nordwall, J.; Team, P.C.S. A randomized, controlled trial of Ebola virus disease therapeutics. N. Engl. J. Med. 2019, 381, 2293–2303.
[17]	Levine, M.M. Monoclonal antibody therapy for Ebola virus disease. N. Engl. J. Med. 2019, 381, 2365–2366.
[18]	AstraZeneca [Internet]. Our priorities in responding to the COVID-19 outbreak. [cited 2020 Feb 5]. Available from: https://www.astrazeneca.com/media-centre/articles/2020/ our-update-on-COVID-19. html.
[19]	AstraZeneca [Internet]. Researching antibodies to target COVID-19. [cited 2020 Feb 5]. Available from: https://www.astrazeneca.com/media-centre/articles/2020/researching-antibodies-to-target-COVID-19.html#!
[20]	Adaptive[Internet]. Adaptive Biotechnologies and Microsoft expand partnership to decode COVID-19 immune response and provide open data access. [cited 2020 Feb 5]. Available from:https://investors.adaptivebiotech.com/news-releases/news-release-details/adaptive-biotechnologies-and-microsoft-expand-partnership-decode.
[21]	Amgen [Internet]. Amgen And Adaptive Biotechnologies Announce Strategic Partnership To Develop A Therapeutic To Prevent Or Treat COVID-19. [cited 2020 Feb 5]. Available from: https://www.amgen.com/media/news-releases/2020/04/amgen-and-adaptive-biotechnologies-announce-strategic-partnership-to-develop-a-therapeutic-to-prevent-or-treat-COVID-19/.
[22]	Prnasia [Internet]. Pharm Biotechnology and Vir Biotechnology have reached a global research agreement on novel Coronavirus Antibody. [cited 2020 Feb 5]. Available from: https://www.prnasia.com/story/273436-1.shtml.
[23]	GSK [Internet]. GSK and Vir Biotechnology enter collaboration to find coronavirus solutions. [cited 2020 Feb 5]. Available from:https://www.gsk.com/en-gb/media/press-releases/gsk-and-vir-biotechnology-enter-collaboration-to-find-coronavirus-solutions/.
[24]	Fierce [Internet]. Samsung scores $362M deal to help Vir scale up COVID-19 antibody production. [cited 2020 Feb 5]. Available from: https://www.fiercepharma.com/manufacturing/vir-inks-deal-samsung-to-scale-up-COVID-19-antibody-manufacturing.
[25]	Ju B.; Zhang Q.; Ge X.; Wang R.; Yu J.; Shan S. Potent human neutralizing antibodies elicited by SARS-CoV-2 infection. ChemRxiv. [Preprint.] March.21, 2020. [accessed 2020 April 5]. Available from: https://www.biorxiv.org/content/10.1101/2020.03.21.990770v2.
[26]	Briibio [Internet]. Tsinghua University -the Third People’s Hospital of Shenzhen Municipality of has established cooperation with Tengshengbo to jointly develop whole-human monoclonal neutralizing antibody against COVID-19. [cited 2020 Feb 5]. Available from: https://cn.briibio.com/news/57.html.
[27]	Junshipharma [Internet]. Junshi Biology and Institute of Microbiology, CAS. Jointly developed Novel Coronavirus Neutralizing Antibody. [cited 2020 Feb 5]. Available from: http://www.junshipharma.com/News.html.
[28]	Chi, X.; Yan, R.; Zhang, J.; Zhang, G.; Zhang, Y.; Hao, M.; Zhang, Z.; Fan, P.; Dong, Y.; Yang, Y.; Chen, Z.; Guo, Y.; Zhang, J.; Li, Y.; Song, X.; Chen, Y.; Xia, L.; Fu, L.; Hou, L.; Xu, J.; Yu, C.; Li, J.; Zhou, Q.; Chen, W. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science. 2020, 369, 650–655.
[29]	Wang, Q.H.; Zhang, Y.F.; Wu, L.L.; Niu, S.; Song, C.L.; Zhang, Z.Y.; Lu, G.W.; Qiao, C.P.; Hu, Y.; Yuen, K.Y.; Wang, Q.S.; Zhou, H.; Yan, J.H.; Qi, J.X. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell. 2020, 181, 894–904.e9.
[30]	Watanabe, Y.; Allen, J.D.; Wrapp, D.; McLellan, J.S.; Crispin, M. Site-specific glycan analysis of the SARS-CoV-2 spike. Science. 2020, 369, 330–333.
[31]	Zhang, Y.; Zhao, W.J.; Mao, Y.H.; Wang, S.S.; Yang, H. Site-specific N-glycosylation characterization of recombinant SARS-CoV-2 spike proteins using high-resolution mass spectrometry. 2020.
[32]	Chi, X.; Yan, R.; Zhang, J.; Zhang, G.; Zhang, Y.; Hao, M.; Zhang, Z.; Fan, P.; Dong, Y.; Yang, Y.; Chen, Z.; Guo, Y.; Zhang, J.; Li, Y.; Song, X.; Chen, Y.; Xia, L.; Fu, L.; Hou, L.; Xu, J.; Yu, C.; Li, J.; Zhou, Q.; Chen, W. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science. 2020, 369, 650–655.
[33]	Zhang, B.; Zhou, X.; Zhu, C.; Song, Y.; Feng, F.; Qiu, Y.; Feng, J.; Jia, Q.; Song, Q.; Zhu, B.; Wang, J. Immune phenotyping based on the neutrophil-to-lymphocyte ratio and IgG level predicts disease severity and outcome for patients with COVID-19. Front Mol Biosci 2020, 7, 157.
[34]	Baxt, B.; Mason, P.W. Foot-and-mouth disease virus undergoes restricted replication in macrophage cell cultures following fc receptor-mediated adsorption. Virology. 1995, 207, 503–509.
[35]	Wang, S.; Peng, Y.; Wang, R.; Jiao, S.; Wang, M.; Huang, W.; Shan, C.; Jiang, W.; Li, Z.; Gu, C.; Chen, B.; Hu, X.; Yao, Y.; Min, J.; Zhang, H.; Chen, Y.; Gao, G.; Tang, P.; Li, G.; Wang, A.; Wang, L.; Zhang, J.; Chen, S.; Gui, X.; Yuan, Z.; Liu, D. Characterization of neutralizing antibody with prophylactic and therapeutic efficacy against SARS-CoV-2 in rhesus monkeys. Nat. Commun. 2020, 11, 5752.
[36]	Wu, F.; Yan, R.; Liu, M.; Liu, Z.; Wang, Y.; Luan, D. Antibody-dependent enhancement (ADE) of SARS-CoV-2 infection in recovered COVID-19 patients: studies based on cellular and structural biology analysis. medRxiv. [Preprint.]. October 13, 2020.[accessed 2020 October 30]. Available from: https://www.medrxiv.org/content/10.1101/ 2020.10.08.20209114v1.
[37]	Zhou, Y.J.; Liu, Z.Z.; Li, S.B.; Xu, W.; Zhang, Q.Q.; Silva, I.T.; Li, C.; Wu, Y.L.; Jiang, Q.L.; Liu, Z.M.; Wang, Q.J.; Guo, Y.; Wu, J.B.; Gu, C.J.; Cai, X.; Qu, D.; Mayer, C.T.; Wang, X.X.; Wang, Q. Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD. Cell Rep. 2021, 34, 108699.
[38]	Liu, Y.; Tuck Soh, W.; Tada, A.; Arakawa, A.; Matsuoka, S.; Nakayama, E. An infectivity-enhancing site on the SARS-CoV-2 spike protein is targeted by COVID-19 patient antibodies. medRxiv. [Preprint.]. December 18, 2020. [accessed 2020 December 30]. Available from: https://www.biorxiv.org/content/10.1101/2020.12.18. 423358v1.
[39]	Li, D.; Edwards, R.; Manne, K.; Martinez, D.; Schäfer, A.; Munir Alam, S. The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates. medRxiv. [Preprint.]. January 02, 2021. [accessed 2020 January 30]. Available from: https://www.biorxiv.org/content/10.1101/2020.12.31. 424729v1.
[40]	Halstead, S.B.; Mahalingam, S.; Marovich, M.A.; Ubol, S.; Mosser, D.M. Intrinsic antibody-dependent enhancement of microbial infection in macrophages: disease regulation by immune complexes. Lancet Infect. Dis. 2010, 10, 712–722.
[41]	Cao, X. COVID-19: immunopathology and its implications for therapy. Nat. Rev. Immunol. 2020, 20, 269–270.
[42]	Zhao, J.J.; Yuan, Q.; Wang, H.Y.; Liu, W.; Liao, X.J.; Su, Y.Y.; Wang, X.; Yuan, J.; Li, T.D.; Li, J.X.; Qian, S.; Hong, C.M.; Wang, F.X.; Liu, Y.X.; Wang, Z.Q.; He, Q.; Li, Z.Y.; He, B.; Zhang, T.Y.; Fu, Y.; Ge, S.X.; Liu, L.; Zhang, J.; Xia, N.S.; Zhang, Z. Antibody responses to SARS-CoV-2 in patients with novel coronavirus disease 2019. Clin. Infect. Dis. 2020, 71, 2027–2034.
[43]	Liu, L.; Wei, Q.; Lin, Q.; Fang, J.; Wang, H.; Kwok, H.; Tang, H.; Nishiura, K.; Peng, J.; Tan, Z.; Wu, T.; Cheung, K.W.; Chan, K.H.; Alvarez, X.; Qin, C.; Lackner, A.; Perlman, S.; Yuen, K.Y.; Chen, Z. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight. 2019, 4. DOI:10.1172/jci.insight.123158.
[44]	Gao, Q.; Bao, L.L.; Mao, H.Y.; Wang, L.; Xu, K.W.; Yang, M.N.; Li, Y.J.; Zhu, L.; Wang, N.; Lv, Z.; Gao, H.; Ge, X.Q.; Kan, B.; Hu, Y.L.; Liu, J.N.; Cai, F.; Jiang, D.Y.; Yin, Y.H.; Qin, C.F.; Li, J.; Gong, X.J.; Lou, X.Y.; Shi, W.; Wu, D.D.; Zhang, H.M.; Zhu, L.; Deng, W.; Li, Y.R.; Lu, J.X.; Li, C.G.; Wang, X.X.; Yin, W.D.; Zhang, Y.J.; Qin, C. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020, 369, 77–81.
[45]	Rogers, T.F.; Zhao, F.; Huang, D.; Beutler, N.; Burns, A.; He, W.T.; Limbo, O.; Smith, C.; Song, G.; Woehl, J.; Yang, L.; Abbott, R.K.; Callaghan, S.; Garcia, E.; Hurtado, J.; Parren, M.; Peng, L.; Ramirez, S.; Ricketts, J.; Ricciardi, M.J.; Rawlings, S.A.; Wu, N.C.; Yuan, M.; Smith, D.M.; Nemazee, D.; Teijaro, J.R.; Voss, J.E.; Wilson, I.A.; Andrabi, R.; Briney, B.; Landais, E.; Sok, D.; Jardine, J.G.; Burton, D.R. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science. 2020, 369, 956–963.
[46]	Cao, Y.L.; Su, B.; Guo, X.H.; Sun, W.J.; Deng, Y.Q.; Bao, L.L.; Zhu, Q.Y.; Zhang, X.; Zheng, Y.H.; Geng, C.Y.; Chai, X.R.; He, R.S.; Li, X.F.; Lv, Q.; Zhu, H.; Deng, W.; Xu, Y.F.; Wang, Y.J.; Xie, X.S. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell. 2020, 182, 73–84.e16.
[47]	Wu, Y.; Wang, F.; Shen, C.; Peng, W.; Li, D.; Zhao, C. A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2. Science. 2020, 368, 1274–1278.
[48]	Liu, X.; Gao, F.; Gou, L.; Chen, Y.; Gu, Y.; Ao, L. Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection. ChemRxiv. [Preprint.] May 04, 2020. [accessed 2020 June 14]. Available from: https://www.biorxiv.org/content/ 10.1101/2020.05.03.074914v2.
[49]	Brouwer, P.J.M.; Caniels, T.G.; van der Straten, K.; Snitselaar, J.L.; Aldon, Y.; Bangaru, S.; Torres, J.L.; Okba, N.M.A.; Claireaux, M.; Kerster, G.; Bentlage, A.E.H.; van Haaren, M.M.; Guerra, D.; Burger, J.A.; Schermer, E.E.; Verheul, K.D.; van der Velde, N.; van der Kooi, A.; van Schooten, J.; van Breemen, M.J.; Bijl, T.P.L.; Sliepen, K.; Aartse, A.; Derking, R.; Bontjer, I.; Kootstra, N.A.; Wiersinga, W.J.; Vidarsson, G.; Haagmans, B.L.; Ward, A.B.; de Bree, G.J.; Sanders, R.W.; van Gils, M.J. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020, 369, 643–650.
[50]	Chi, X.; Yan, R.; Zhang, J.; Zhang, G.; Zhang, Y.; Hao, M.; Zhang, Z.; Fan, P.; Dong, Y.; Yang, Y.; Chen, Z.; Guo, Y.; Zhang, J.; Li, Y.; Song, X.; Chen, Y.; Xia, L.; Fu, L.; Hou, L.; Xu, J.; Yu, C.; Li, J.; Zhou, Q.; Chen, W. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science. 2020, 369, 650–655.
[51]	Wang, P.; Liu, L.; Nair, M.S.; Yin, M.T.; Luo, Y.; Wang, Q. SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease. Emerg. Microbes. Infect. 2020, 9, 2091–2093.
[52]	Liu, L.; Wang, P.; Nair, M.S.; Yu, J.; Rapp, M.; Wang, Q.; Luo, Y.; Chan, J.F.; Sahi, V.; Figueroa, A.; Guo, X.V.; Cerutti, G.; Bimela, J.; Gorman, J.; Zhou, T.; Chen, Z.; Yuen, K.Y.; Kwong, P.D.; Sodroski, J.G.; Yin, M.T.; Sheng, Z.; Huang, Y.; Shapiro, L.; Ho, D.D. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature. 2020, 584, 450–456.
[53]	Caifuhao [Internet]. US pauses Eli Lilly’s trial of a coronavirus antibody treatment over safety concerns. Health and Science, Oct 13, 2020. [cited 2020 Feb 5]. Available from: http://caifuhao.eastmoney.com/news/ 20201015093547254047210.
[54]	Sun, Y.P.; Ho, M. Emerging antibody-based therapeutics against SARS-CoV-2 during the global pandemic. Antibody Ther. 2020, 3, 246–256.

中和抗体在新型冠状病毒肺炎治疗中的重要意义: 进展与展望

Significance of neutralizing antibodies in COVID-19 therapy: progress and prospect

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