Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

Rongtao Lai , Tianhui Zhou , Xiaogang Xiang , Jie Lu , Haiguang Xin , Qing Xie

Front. Med. ›› 2021, Vol. 15 ›› Issue (4) : 644 -648.

PDF (311KB)
Front. Med. ›› 2021, Vol. 15 ›› Issue (4) : 644 -648. DOI: 10.1007/s11684-021-0847-4
LETTER TO FRONTIERS OF MEDICINE
LETTER TO FRONTIERS OF MEDICINE

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

Author information +
History +
PDF (311KB)

Abstract

The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

Keywords

neutralizing antibody / antibody cocktail / SARS-CoV-2 / COVID-19 / therapeutic strategy

Cite this article

Download citation ▾
Rongtao Lai, Tianhui Zhou, Xiaogang Xiang, Jie Lu, Haiguang Xin, Qing Xie. Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections. Front. Med., 2021, 15(4): 644-648 DOI:10.1007/s11684-021-0847-4

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Bedford J, Enria D, Giesecke J, Heymann DL, Ihekweazu C, Kobinger G, Lane HC, Memish Z, Oh MD, Sall AA, Schuchat A, Ungchusak K, Wieler LH; WHO Strategic and Technical Advisory Group for Infectious Hazards. COVID-19: towards controlling of a pandemic. Lancet 2020; 395(10229): 1015–1018

[2]

Ali MJ, Hanif M, Haider MA, Ahmed MU, Sundas F, Hirani A, Khan IA, Anis K, Karim AH. Treatment options for COVID-19: a review. Front Med (Lausanne) 2020; 7: 480

[3]

Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, Wu Y, Xiao W, Liu S, Chen E, Chen W, Wang X, Yang J, Lin J, Zhao Q, Yan Y, Xie Z, Li D, Yang Y, Liu L, Qu J, Ning G, Shi G, Xie Q. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ 2020; 369: m1849

[4]

Mulangu S, Dodd LE, Davey RT Jr, Tshiani Mbaya O, Proschan M, Mukadi D, Lusakibanza Manzo M, Nzolo D, Tshomba Oloma A, Ibanda A, Ali R, Coulibaly S, Levine AC, Grais R, Diaz J, Lane HC, Muyembe-Tamfum JJ; PALM Writing Group, 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, Valllée D, Nordwall J; PALM Consortium Study Team. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med 2019; 381(24): 2293–2303

[5]

Ho M. Perspectives on the development of neutralizing antibodies against SARS-CoV-2. Antib Ther 2020; 3(2): 109–114

[6]

Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020; 367(6485): 1444–1448

[7]

Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with Covid-19. N Engl J Med 2020; 382(17): 1653–1659

[8]

Brouwer PJM, Caniels TG, van der Straten K, Snitselaar JL, Aldon Y, Bangaru S, Torres JL, Okba NMA, Claireaux M, Kerster G, Bentlage AEH, van Haaren MM, Guerra D, Burger JA, Schermer EE, Verheul KD, van der Velde N, van der Kooi A, van Schooten J, van Breemen MJ, Bijl TPL, Sliepen K, Aartse A, Derking R, Bontjer I, Kootstra NA, Wiersinga WJ, Vidarsson G, Haagmans BL, Ward AB, de Bree GJ, Sanders RW, van Gils MJ. Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science 2020; 369(6504): 643–650

[9]

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(6504): 650–655

[10]

Pinto D, Park YJ, Beltramello M, Walls AC, Tortorici MA, Bianchi S, Jaconi S, Culap K, Zatta F, De Marco A, Peter A, Guarino B, Spreafico R, Cameroni E, Case JB, Chen RE, Havenar-Daughton C, Snell G, Telenti A, Virgin HW, Lanzavecchia A, Diamond MS, Fink K, Veesler D, Corti D. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 2020; 583(7815): 290–295

[11]

Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L, Zhu Q, Zhang X, Zheng Y, Geng C, Chai X, He R, Li X, Lv Q, Zhu H, Deng W, Xu Y, Wang Y, Qiao L, Tan Y, Song L, Wang G, Du X, Gao N, Liu J, Xiao J, Su XD, Du Z, Feng Y, Qin C, Qin C, Jin R, Xie XS. Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells. Cell 2020; 182(1): 73–84.e16

[12]

Du S, Cao Y, Zhu Q, Yu P, Qi F, Wang G, Du X, Bao L, Deng W, Zhu H, Liu J, Nie J, Zheng Y, Liang H, Liu R, Gong S, Xu H, Yisimayi A, Lv Q, Wang B, He R, Han Y, Zhao W, Bai Y, Qu Y, Gao X, Ji C, Wang Q, Gao N, Huang W, Wang Y, Xie XS, Su XD, Xiao J, Qin C. Structurally resolved SARS-CoV-2 antibody shows high efficacy in severely infected hamsters and provides a potent cocktail pairing strategy. Cell 2020; 183(4): 1013–1023.e13

[13]

Kreer C, Zehner M, Weber T, Ercanoglu MS, Gieselmann L, Rohde C, Halwe S, Korenkov M, Schommers P, Vanshylla K, Di Cristanziano V, Janicki H, Brinker R, Ashurov A, Krähling V, Kupke A, Cohen-Dvashi H, Koch M, Eckert JM, Lederer S, Pfeifer N, Wolf T, Vehreschild MJGT, Wendtner C, Diskin R, Gruell H, Becker S, Klein F. Longitudinal isolation of potent near-germline SARS-CoV-2-neutralizing antibodies from COVID-19 patients. Cell 2020; 182(4): 843–854.e12

[14]

Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol 2020; 5(10): 1185–1191

[15]

Karthik K, Senthilkumar TMA, Udhayavel S, Raj GD. Role of antibody-dependent enhancement (ADE) in the virulence of SARS-CoV-2 and its mitigation strategies for the development of vaccines and immunotherapies to counter COVID-19. Hum Vaccin Immunother 2020; 16(12): 3055–3060

[16]

Cohen J. HIV/AIDS. Prevention cocktails: combining tools to stop HIV’s spread. Science 2005; 309(5737): 1002–1005

[17]

Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ. Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 2010; 60(3): 166–193

[18]

Ledford H. Cocktails for cancer with a measure of immunotherapy. Nature 2016; 532(7598): 162–164

[19]

Andrews CD, Huang Y, Ho DD, Liberatore RA. In vivo expressed biologics for infectious disease prophylaxis: rapid delivery of DNA-based antiviral antibodies. Emerg Microbes Infect 2020; 9(1): 1523–1533

[20]

Jones BE, Brown-Augsburger PL, Corbett KS, Westendorf K, Davies J, Cujec TP, Wiethoff CM, Blackbourne JL, Heinz BA, Foster D, Higgs RE, Balasubramaniam D, Wang L, Bidshahri R, Kraft L, Hwang Y, Žentelis S, Jepson KR, Goya R, Smith MA, Collins DW, Hinshaw SJ, Tycho SA, Pellacani D, Xiang P, Muthuraman K, Sobhanifar S, Piper MH, Triana FJ, Hendle J, Pustilnik A, Adams AC, Berens SJ, Baric RS, Martinez DR, Cross RW, Geisbert TW, Borisevich V, Abiona O, Belli HM, de Vries M, Mohamed A, Dittmann M, Samanovic M, Mulligan MJ, Goldsmith JA, Hsieh CL, Johnson NV, Wrapp D, McLellan JS, Barnhart BC, Graham BS, Mascola JR, Hansen CL, Falconer E. LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection. bioRxiv 2020; [Preprint] doi:10.1101/2020.09.30.318972

[21]

Hansen J, Baum A, Pascal KE, Russo V, Giordano S, Wloga E, Fulton BO, Yan Y, Koon K, Patel K, Chung KM, Hermann A, Ullman E, Cruz J, Rafique A, Huang T, Fairhurst J, Libertiny C, Malbec M, Lee WY, Welsh R, Farr G, Pennington S, Deshpande D, Cheng J, Watty A, Bouffard P, Babb R, Levenkova N, Chen C, Zhang B, Romero Hernandez A, Saotome K, Zhou Y, Franklin M, Sivapalasingam S, Lye DC, Weston S, Logue J, Haupt R, Frieman M, Chen G, Olson W, Murphy AJ, Stahl N, Yancopoulos GD, Kyratsous CA. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 2020; 369(6506): 1010–1014

[22]

Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med 2021; 384(3): 238–251

[23]

ter Meulen J, van den Brink EN, Poon LL, Marissen WE, Leung CS, Cox F, Cheung CY, Bakker AQ, Bogaards JA, van Deventer E, Preiser W, Doerr HW, Chow VT, de Kruif J, Peiris JS, Goudsmit J. Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med 2006; 3(7): e237

RIGHTS & PERMISSIONS

Higher Education Press

AI Summary AI Mindmap
PDF (311KB)

3261

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/