Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein

Science Translational Medicine

Volumn 6, Issue 234, 2014, Pages

  Jiang, Liwei ^a   Wang, Nianshuang ^b   Zuo, Teng ^a,b   Shi, Xuanling ^a   Poon, Kwok Man Vincent ^c   Wu, Yongkang ^d   Gao, Fei ^a   Li, Danyang ^a   Wang, Ruoke ^a   Guo, Jianying ^a   Fu, Lili ^a   Yuen, Kwok Yung ^c   Zheng, Bo Jian ^c   Wang, Xinquan ^b   Zhang, Linqi ^a  

^a Tsinghua University   (China)

^b TSINGHUA UNIVERSITY   (China)

^c UNIVERSITY OF HONG KONG   (Hong Kong)

^d SICHUAN UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CORONAVIRUS SPIKE GLYCOPROTEIN; DIPEPTIDYL PEPTIDASE IV; HUMAN MONOCLONAL ANTIBODY; IMMUNOGLOBULIN G1 ANTIBODY; MONOCLONAL ANTIBODY MIDDLE EAST RESPIRATORY SYNDROME 27; MONOCLONAL ANTIBODY MIDDLE EAST RESPIRATORY SYNDROME 4; NEUTRALIZING ANTIBODY; SINGLE CHAIN FRAGMENT VARIABLE ANTIBODY; UNCLASSIFIED DRUG; MONOCLONAL ANTIBODY; VIRUS ANTIBODY;

ANIMAL CELL; ARTICLE; BINDING AFFINITY; CHEMICAL ANALYSIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORONAVIRUS; DRUG ISOLATION; DRUG POTENTIATION; DRUG SCREENING; EPITOPE MAPPING; HUMAN; HUMAN CELL; IMMUNOASSAY; INFECTION PREVENTION; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; PSEUDOTYPING; RECEPTOR BINDING; RECEPTOR BLOCKING; VIRUS ENTRY; VIRUS ENVELOPE; VIRUS ISOLATION; VIRUS NEUTRALIZATION; IC50; IMMUNOLOGY; PHYSIOLOGY;

ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; HUMANS; INHIBITORY CONCENTRATION 50; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS;

EID: 84899797757     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3008140     Document Type: Article

References (49)

1. J. F. Chan, K. S. Li, K. K. To, V. C. Cheng, H. Chen, K. Y. Yuen, Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? J. Infect. 65, 477-489 (2012).
2. A. Bermingham, M. A. Chand, C. S. Brown, E. Aarons, C. Tong, C. Langrish, K. Hoschler, K. Brown, M. Galiano, R. Myers, R. G. Pebody, H. K. Green, N. L. Boddington, R. Gopal, N. Price, W. Newsholme, C. Drosten, R. A. Fouchier, M. Zambon, Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Euro Surveill. 17, 20290 (2012).
3. R. J. de Groot, S. C. Baker, R. S. Baric, C. S. Brown, C. Drosten, L. Enjuanes, R. A. Fouchier, M. Galiano, A. E. Gorbalenya, Z. Memish, S. Perlman, L. L. Poon, E. J. Snijder, G. M. Stephens, P. C. Woo, A. M. Zaki, M. Zambon, J. Ziebuhr, Middle East respiratory syndrome coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group. J. Virol. 87, 7790-7792 (2013).
4. V. S. Raj, H. Mou, S. L. Smits, D. H. Dekkers, M. A. Müller, R. Dijkman, D. Muth, J. A. Demmers, A. Zaki, R. A. Fouchier, V. Thiel, C. Drosten, P. J. Rottier, A. D. Osterhaus, B. J. Bosch, B. L. Haagmans, Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495, 251-254 (2013).
5. The WHO MERS-CoV Research Group, State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans. PLOS Curr. 5, ecurrents.outbreaks.0bf719e352e7478f8ad85fa30127d (2013).
6. A. M. Zaki, S. van Boheemen, T. M. Bestebroer, A. D. Osterhaus, R. A. Fouchier, Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 367, 1814-1820 (2012).
7. L. Du, Y. He, Y. Zhou, S. Liu, B. J. Zheng, S. Jiang, The spike protein of SARS-CoV - A target for vaccine and therapeutic development. Nat. Rev. Microbiol. 7, 226-236 (2009).
8. R. L. Graham, E. F. Donaldson, R. S. Baric, A decade after SARS: Strategies for controlling emerging coronaviruses. Nat. Rev. Microbiol. 11, 836-848 (2013).
9. Z. A. Memish, N. Mishra, K. J. Olival, S. F. Fagbo, V. Kapoor, J. H. Epstein, R. Alhakeem, A. Durosinloun, M. Al Asmari, A. Islam, A. Kapoor, T. Briese, P. Daszak, A. A. Al Rabeeah, W. I. Lipkin, Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg. Infect. Dis. 19, 1819-1823 (2013).
10. N. M. Ferguson, M. D. Van Kerkhove, Identification of MERS-CoV in dromedary camels. Lancet Infect. Dis. 14, 93-94 (2014).
11. B. L. Haagmans, S. H. Al Dhahiry, C. B. Reusken, V. S. Raj, M. Galiano, R. Myers, G. J. Godeke, M. Jonges, E. Farag, A. Diab, H. Ghobashy, F. Alhajri, M. Al-Thani, S. A. Al-Marri, H. E. Al Romaihi, A. Al Khal, A. Bermingham, A. D. Osterhaus, M. M. AlHajri, M. P. Koopmans, Middle East respiratory syndrome coronavirus in dromedary camels: An outbreak investigation. Lancet Infect. Dis. 14, 140-145 (2014).
12. R. A. Perera, P. Wang, M. R. Gomaa, R. El-Shesheny, A. Kandeil, O. Bagato, L. Y. Siu, M. M. Shehata, A. S. Kayed, Y. Moatasim, M. Li, L. L. Poon, Y. Guan, R. J. Webby, M. A. Ali, J. S. Peiris, G. Kayali, Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill. 18, 20574 (2013).
13. C. B. Reusken, B. L. Haagmans, M. A. Müller, C. Gutierrez, G. J. Godeke, B. Meyer, D. Muth, V. S. Raj, L. Smits-De Vries, V. M. Corman, J. F. Drexler, S. L. Smits, Y. E. El Tahir, R. De Sousa, J. van Beek, N. Nowotny, K. van Maanen, E. Hidalgo-Hermoso, B. J. Bosch, P. Rottier, A. Osterhaus, C. Gortázar-Schmidt, C. Drosten, M. P. Koopmans, Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: A comparative serological study. Lancet Infect. Dis. 13, 859-866 (2013).
14. M. Cotten, S. J. Watson, P. Kellam, A. A. Al-Rabeeah, H. Q. Makhdoom, A. Assiri, J. A. Al-Tawfiq, R. F. Alhakeem, H. Madani, F. A. AlRabiah, S. Al Hajjar, W. N. Al-nassir, A. Albarrak, H. Flemban, H. H. Balkhy, S. Alsubaie, A. L. Palser, A. Gall, R. Bashford-Rogers, A. Rambaut, A. I. Zumla, Z. A. Memish, Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: A descriptive genomic study. Lancet 382, 1993-2002 (2013).
15. S. K. Lau, K. S. Li, A. K. Tsang, C. S. Lam, S. Ahmed, H. Chen, K. H. Chan, P. C. Woo, K. Y. Yuen, Genetic characterization of Betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of Pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: Implications for the origin of the novel Middle East respiratory syndrome coronavirus. J. Virol. 87, 8638-8650 (2013).
16. S. van Boheemen, M. de Graaf, C. Lauber, T. M. Bestebroer, V. S. Raj, A. M. Zaki, A. D. Osterhaus, B. L. Haagmans, A. E. Gorbalenya, E. J. Snijder, R. A. Fouchier, Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio 3, e00473-12 (2012).
17. P. C. Y. Woo, S. K. P. Lau, K. S. M. Li, A. K. L. Tsang, K. Y. Yuen, Genetic relatedness of the novel human group C betacoronavirus to Tylonycteris bat coronavirus HKU4 and Pipistrellus bat coronavirus HKU5. Emerg. Microbes Infect. 1, e35 (2012).
18. J. F. Chan, K. K. To, H. Tse, D. Y. Jin, K. Y. Yuen, Interspecies transmission and emergence of novel viruses: Lessons from bats and birds. Trends Microbiol. 21, 544-555 (2013).
19. J. F. Chan, K. H. Chan, G. K. Choi, K. K. To, H. Tse, J. P. Cai, M. L. Yeung, V. C. Cheng, H. Chen, X. Y. Che, S. K. Lau, P. C. Woo, K. Y. Yuen, Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: Implications for disease pathogenesis and clinical manifestation. J. Infect. Dis. 207, 1743-1752 (2013).
20. P. C. Woo, M. Wang, S. K. Lau, H. Xu, R. W. Poon, R. Guo, B. H. Wong, K. Gao, H. W. Tsoi, Y. Huang, K. S. Li, C. S. Lam, K. H. Chan, B. J. Zheng, K. Y. Yuen, Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features. J. Virol. 81, 1574-1585 (2007).
21. Z. A. Memish, A. I. Zumla, R. F. Al-Hakeem, A. A. Al-Rabeeah, G. M. Stephens, Family cluster of Middle East respiratory syndrome coronavirus infections. N. Engl. J. Med. 368, 2487-2494 (2013).
22. A. Assiri, A. McGeer, T. M. Perl, C. S. Price, A. A. Al Rabeeah, D. A. Cummings, Z. N. Alabdullatif, M. Assad, A. Almulhim, H. Makhdoom, H. Madani, R. Alhakeem, J. A. Al-Tawfiq, M. Cotten, S. J. Watson, P. Kellam, A. I. Zumla, Z. A. Memish; KSA MERS-CoV Investigation Team, Hospital outbreak of Middle East respiratory syndrome coronavirus. N. Engl. J. Med. 369, 407-416 (2013).
23. D. Falzarano, E. de Wit, A. L. Rasmussen, F. Feldmann, A. Okumura, D. P. Scott, D. Brining, T. Bushmaker, C. Martellaro, L. Baseler, A. G. Benecke, M. G. Katze, V. J. Munster, H. Feldmann, Treatment with interferon-a2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 19, 1313-1317 (2013).
24. J. A. Al-Tawfiq, H. Momattin, J. Dib, Z. A. Memish, Ribavirin and interferon therapy in patients infected with the Middle East respiratory syndrome coronavirus: An observational study. Int. J. Infect. Dis. 20, 42-46 (2014).
25. J. F. Chan, K. H. Chan, R. Y. Kao, K. K. To, B. J. Zheng, C. P. Li, P. T. Li, J. Dai, F. K. Mok, H. Chen, F. G. Hayden, K. Y. Yuen, Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J. Infect. 67, 606-616 (2013).
26. L. Lu, Q. Liu, Y. Zhu, K. H. Chan, L. Qin, Y. Li, Q. Wang, J. F. Chan, L. Du, F. Yu, C. Ma, S. Ye, K. Y. Yuen, R. Zhang, S. Jiang, Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat. Commun. 5, 3067 (2014).
27. S. K. Lau, C. C. Lau, K. H. Chan, C. P. Li, H. Chen, D. Y. Jin, J. F. Chan, P. C. Woo, K. Y. Yuen, Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: Implications for pathogenesis and treatment. J. Gen. Virol. 94, 2679-2690 (2013).
28. J. Zhou, H. Chu, C. Li, B. H. Wong, Z. S. Cheng, V. K. Poon, T. Sun, C. C. Lau, K. K. Wong, J. Y. Chan, J. F. Chan, K. K. To, K. H. Chan, B. J. Zheng, K. Y. Yuen, Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: Implications for pathogenesis. J. Infect. Dis. 209, 1331-1342 (2014).
29. P. S. Masters, The molecular biology of coronaviruses. Adv. Virus Res. 66, 193-292 (2006).
30. S. R. Weiss, S. Navas-Martin, Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol. Mol. Biol. Rev. 69, 635-664 (2005).
31. K. H. Chan, J. F. Chan, H. Tse, H. Chen, C. C. Lau, J. P. Cai, A. K. Tsang, X. Xiao, K. K. To, S. K. Lau, P. C. Woo, B. J. Zheng, M. Wang, K. Y. Yuen, Cross-reactive antibodies in convalescent SARS patients' sera against the emerging novel human coronavirus EMC (2012) by both immunofluorescent and neutralizing antibody tests. J. Infect. 67, 130-140 (2013).
32. G. Lu, Y. Hu, Q. Wang, J. Qi, F. Gao, Y. Li, Y. Zhang, W. Zhang, Y. Yuan, J. Bao, B. Zhang, Y. Shi, J. Yan, G. F. Gao, Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature 500, 227-231 (2013).
33. N. Wang, X. Shi, L. Jiang, S. Zhang, D. Wang, P. Tong, D. Guo, L. Fu, Y. Cui, X. Liu, K. C. Arledge, Y. H. Chen, L. Zhang, X. Wang, Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 23, 986-993 (2013).
34. K. Ohnuma, B. L. Haagmans, R. Hatano, V. S. Raj, H. Mou, S. Iwata, N. H. Dang, B. Jan Bosch, C. Morimoto, Inhibition of Middle East respiratory syndrome coronavirus infection by anti-CD26 monoclonal antibody. J. Virol. 87, 13892-13899 (2013).
35. K. Ohnuma, N. H. Dang, C. Morimoto, Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol. 29, 295-301 (2008).
36. L. Du, Z. Kou, C. Ma, X. Tao, L. Wang, G. Zhao, Y. Chen, F. Yu, C. T. Tseng, Y. Zhou, S. Jiang, A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: Implication for developing therapeutics and vaccines. PLOS One 8, e81587 (2013).
37. L. Du, G. Zhao, Z. Kou, C. Ma, S. Sun, V. K. Poon, L. Lu, L. Wang, A. K. Debnath, B. J. Zheng, Y. Zhou, S. Jiang, Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development. J. Virol. 87, 9939-9942 (2013).
38. F. Song, R. Fux, L. B. Provacia, A. Volz, M. Eickmann, S. Becker, A. D. Osterhaus, B. L. Haagmans, G. Sutter, Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus ankara efficiently induces virus-neutralizing antibodies. J. Virol. 87, 11950-11954 (2013).
39. H. Mou, V. S. Raj, F. J. van Kuppeveld, P. J. Rottier, B. L. Haagmans, B. J. Bosch, The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J. Virol. 87, 9379-9383 (2013).
40. G. Chao, W. L. Lau, B. J. Hackel, S. L. Sazinsky, S. M. Lippow, K. D. Wittrup, Isolating and engineering human antibodies using yeast surface display. Nat. Protoc. 1, 755-768 (2006).
41. M. J. Feldhaus, R. W. Siegel, L. K. Opresko, J. R. Coleman, J. M. Feldhaus, Y. A. Yeung, J. R. Cochran, P. Heinzelman, D. Colby, J. Swers, C. Graff, H. S. Wiley, K. D. Wittrup, Flow-cytometric isolation of human antibodies from a nonimmune Saccharomyces cerevisiae surface display library. Nat. Biotechnol. 21, 163-170 (2003).
42. T. C. Chou, Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70, 440-446 (2010).
43. T. C. Chou, P. Talalay, Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22, 27-55 (1984).
44. Z. Keck, W. Wang, Y. Wang, P. Lau, T. H. Carlsen, J. Prentoe, J. Xia, A. H. Patel, J. Bukh, S. K. Foung, Cooperativity in virus neutralization by human monoclonal antibodies to two adjacent regions located at the amino terminus of hepatitis C virus E2 glycoprotein. J. Virol. 87, 37-51 (2013).
45. A. Assiri, J. A. Al-Tawfiq, A. A. Al-Rabeeah, F. A. Al-Rabiah, S. Al-Hajjar, A. Al-Barrak, H. Flemban, W. N. Al-Nassir, H. H. Balkhy, R. F. Al-Hakeem, H. Q. Makhdoom, A. I. Zumla, Z. A. Memish, Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study. Lancet Infect. Dis. 13, 752-761 (2013).
46. P. C. Wilson, S. F. Andrews, Tools to therapeutically harness the human antibody response. Nat. Rev. Immunol. 12, 709-719 (2012).
47. R. L. Graham, R. S. Baric, Recombination, reservoirs, and the modular spike: Mechanisms of coronavirus cross-species transmission. J. Virol. 84, 3134-3146 (2010).
48. B. J. Zheng, K. W. Chan, Y. P. Lin, G. Y. Zhao, C. Chan, H. J. Zhang, H. L. Chen, S. S. Wong, S. K. Lau, P. C. Woo, K. H. Chan, D. Y. Jin, K. Y. Yuen, Delayed antiviral plus immunomodulator treatment still reduces mortality in mice infected by high inoculum of influenza A/H5N1 virus. Proc. Natl. Acad. Sci. U.S.A. 105, 8091-8096 (2008).
49. L. Du, Y. He, Y. Wang, H. Zhang, S. Ma, C. K. Wong, S. H. Wu, F. Ng, J. D. Huang, K. Y. Yuen, S. Jiang, Y. Zhou, B. J. Zheng, Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S protein elicits neutralizing antibodies: Implication for developing SARS vaccines. Virology 353, 6-16 (2006).