A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates

Science Translational Medicine

Volumn 7, Issue 301, 2015, Pages

  Muthumani, Karuppiah ^a   Falzarano, Darryl ^b,g   Reuschel, Emma L ^a   Tingey, Colleen ^a   Flingai, Seleeke ^a   Villarreal, Daniel O ^a   Wise, Megan ^a   Patel, Ami ^a   Izmirly, Abdullah ^a   Aljuaid, Abdulelah ^a   Seliga, Alecia M ^a   Soule, Geoff ^c   Morrow, Matthew ^d   Kraynyak, Kimberly A ^d   Khan, Amir S ^d   Scott, Dana P ^b   Feldmann, Friederike ^b   LaCasse, Rachel ^b   Meade White, Kimberly ^b   Okumura, Atsushi ^e   Ugen, Kenneth E ^f   Sardesai, Niranjan Y ^d   Kim, J Joseph ^d   Kobinger, Gary ^c   Feldmann, Heinz ^b   Weiner, David B ^a   more..

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c PUBLIC HEALTH AGENCY OF CANADA   (Canada)

^d Inovio Pharmaceuticals   (United States)

^e UNIVERSITY OF WASHINGTON   (United States)

^f UNIVERSITY OF SOUTH FLORIDA   (United States)

^g UNIVERSITY OF SASKATCHEWAN   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DNA VACCINE; NEUTRALIZING ANTIBODY; VIRUS SPIKE PROTEIN; VIRUS ANTIBODY;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY RESPONSE; ANTIGEN SPECIFICITY; ARTICLE; BINDING KINETICS; CAMEL; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; HUMORAL IMMUNITY; IMMUNOGENICITY; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; MOUSE; NONHUMAN; PNEUMONIA; PRIMATE; PRIORITY JOURNAL; RHESUS MONKEY; SEROCONVERSION; VACCINATION; VIRUS NEUTRALIZATION; ANIMAL; IMMUNOLOGY;

ANIMALS; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; CAMELUS; MACACA MULATTA; MICE; MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS; VACCINES, DNA;

EID: 84939810764     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aac7462     Document Type: Article

References (53)

1. N. van Doremalen, T. Bushmaker, V. J. Munster, Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions. Euro Surveill. 18, 20590 (2013).
2. A. Petherick, MERS-CoV: In search of answers. Lancet 381, 2069 (2013).
3. 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. A. 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).
4. C. M. Coleman, M. B. Frieman, Emergence of the Middle East respiratory syndrome coronavirus. PLOS Pathog. 9, e1003595 (2013).
5. Z. A. Memish, J. A. Al-Tawfiq, A. Assiri, Hospital-Associated Middle East respiratory syndrome coronavirus infections. N. Engl. J. Med 369, 1761-1762 (2013).
6. C. D. Gomersall, G. M. Joynt, Middle East respiratory syndrome: New disease, old lessons. Lancet 381, 2229-2230 (2013).
7. C. M. Coleman, M. B. Frieman, Coronaviruses: Important emerging human pathogens. J. Virol. 88, 5209-5212 (2014).
8. S. Perlman, The Middle East respiratory syndrome-How worried should we be? MBio 4, e00531-13 (2013).
9. 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).
10. S. Perlman, J. Zhao, Human coronavirus EMC is not the same as severe acute respiratory syndrome coronavirus. MBio 4, e00002-13 (2013).
11. R. Hilgenfeld, M. Peiris, From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses. Antiviral Res. 100, 286-295 (2013).
12. M. A. Müller, V. S. Raj, D. Muth, B. Meyer, S. Kallies, S. L. Smits, R. Wollny, T. M. Bestebroer, S. Specht, T. Suliman, K. Zimmermann, T. Binger, I. Eckerle, M. Tschapka, A. M. Zaki, A. D. Osterhaus, R. A. Fouchier, B. L. Haagmans, C. Drosten, Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. MBio 3, e00515-12 (2012).
13. 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).
14. Z. A. Memish, A. Zumla, J. A. Al-Tawfiq, How great is the risk of Middle East respiratory syndrome coronavirus to the global population? Expert Rev. Anti Infect. Ther. 11, 979-981 (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. 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).
17. M. Cotten, S. J. Watson, A. I. Zumla, H. Q. Makhdoom, A. L. Palser, S. H. Ong, A. A. Al Rabeeah, R. F. Alhakeem, A. Assiri, J. A. Al-Tawfiq, A. Albarrak, M. Barry, A. Shibl, F. A. Alrabiah, S. Hajjar, H. H. Balkhy, H. Flemban, A. Rambaut, P. Kellam, Z. A. Memish, Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus. MBio 5, e01062-13 (2014).
18. L. Jiang,N.Wang, T. Zuo, X. Shi, K.-M. Poon, Y.Wu, F. Gao, D. Li, R.Wang, J. Guo, L. Fu, K.-Y. Yuen, B.-J. Zheng, X. Wang, L. Zhang, Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein. Sci. Transl. Med. 6, 234ra259 (2014).
19. 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).
20. Z.-Y. Yang, W.-P. Kong, Y. Huang, A. Roberts, B. R. Murphy, K. Subbarao, G. J. Nabel, A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature 428, 561-564 (2004).
21. T. Ying, L. Du, T. W. Ju, P. Prabakaran, C. C. Lau, L. Lu, Q. Liu, L. Wang, Y. Feng, Y. Wang, B.-J. Zheng, K.-Y. Yuen, S. Jiang, D. S. Dimitrov, Exceptionally potent neutralization of Middle East respiratory syndrome coronavirus by human monoclonal antibodies. J. Virol. 88, 7796-7805 (2014).
22. L. Josset, V. D. Menachery, L. E. Gralinski, S. Agnihothram, P. Sova, V. S. Carter, B. L. Yount, R. L. Graham, R. S. Baric, M. G. Katze, Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. MBio 4, e00165-13 (2013).
23. D. J. Laddy, J. Yan, A. S. Khan, H. Andersen, A. Cohn, J. Greenhouse, M. Lewis, J. Manischewitz, L. R. King, H. Golding, R. Draghia-Akli, D. B. Weiner, Electroporation of synthetic DNA antigens offers protection in nonhuman primates challenged with highly pathogenic avian influenza virus. J. Virol. 83, 4624-4630 (2009).
24. M. L. Bagarazzi, J. Yan, M. P. Morrow, X. Shen, R. L. Parker, J. C. Lee, M. Giffear, P. Pankhong, A. S. Khan, K. E. Broderick, C. Knott, F. Lin, J. D. Boyer, R. Draghia-Akli, C. J.White, J. J. Kim, D. B. Weiner, N. Y. Sardesai, Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci. Transl. Med. 4, 155ra138 (2012).
25. K. Mallilankaraman, D. J. Shedlock, H. Bao, O. U. Kawalekar, P. Fagone, A. A. Ramanathan, B. Ferraro, J. Stabenow, P. Vijayachari, S. G. Sundaram, N. Muruganandam, G. Sarangan, P. Srikanth, A. S. Khan, M. G. Lewis, J. J. Kim, N. Y. Sardesai, K. Muthumani, D. B. Weiner, A DNA vaccine against Chikungunya virus is protective in mice and induces neutralizing antibodies in mice and nonhuman primates. PLOS Negl. Trop. Dis. 5, e928 (2011).
26. N. Obeng-Adjei,N. A.Hutnick, J. Yan, J. S. Chu,D. J. Myles,M. P. Morrow, N. Y. Sardesai,D. B.Weiner, DNA vaccine cocktail expressing genotype A and C HBV surface and consensus core antigens generates robust cytotoxic and antibody responses in mice and Rhesus macaques. Cancer Gene Ther. 20, 652-662 (2013).
27. D. J. Shedlock, J. Aviles, K. T. Talbott, G. Wong, S. J. Wu, D. O. Villarreal, D. J. Myles, M. A. Croyle, J. Yan, G. P. Kobinger, D. B. Weiner, Induction of broad cytotoxic T cells by protective DNA vaccination against Marburg and Ebola. Mol. Ther. 21, 1432-1444 (2013).
28. D. O. Villarreal, M. C.Wise, J. N.Walters, E. L. Reuschel, M. J. Choi, N. Obeng-Adjei, J. Yan, M. P. Morrow, D. B. Weiner, Alarmin IL-33 acts as an immunoadjuvant to enhance antigenspecific tumor immunity. Cancer Res. 74, 1789-1800 (2014).
29. B. L. Haagmans, A. D. Osterhaus, Neutralizing the MERS coronavirus threat. Sci. Transl. Med. 6, 235fs219 (2014).
30. X.-C. Tang, S. S. Agnihothram, Y. Jiao, J. Stanhope, R. L. Graham, E. C. Peterson, Y. Avnir, A. S. Tallarico, J. Sheehan, Q. Zhu, R. S. Baric, W. A. Marasco, Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution. Proc. Natl. Acad. Sci. U.S.A. 111, E2018-E2026 (2014).
31. Z. Qian, S. R. Dominguez, K. V. Holmes, Role of the spike glycoprotein of human Middle East respiratory syndrome coronavirus (MERS-CoV) in virus entry and syncytia formation. PLOS One 8, e76469 (2013).
32. G. Zhao, L. Du, C.Ma, Y. Li, L. Li, V. K. Poon, L.Wang, F. Yu, B.-J. Zheng, S. Jiang, Y. Zhou, A safe and convenient pseudovirus-based inhibition assay to detect neutralizing antibodies and screen for viral entry inhibitors against the novel human coronavirus MERS-CoV. Virol. J. 10, 266 (2013).
33. D. C. Montefiori, Measuring HIV neutralization in a luciferase reporter gene assay. Methods Mol. Biol. 485, 395-405 (2009).
34. K. Muthumani, S. Flingai, M. Wise, C. Tingey, K. E. Ugen, D. B. Weiner, Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab. Hum. Vaccin. Immunother. 9, 2253-2262 (2013).
35. 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).
36. K. K. To, I. F. Hung, J. F. Chan, K.-Y. Yuen, From SARS coronavirus to novel animal and human coronaviruses. J. Thorac. Dis. 5, S103-S108 (2013).
37. 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).
38. D. Falzarano, E. de Wit, F. Feldmann, A. L. Rasmussen, A. Okumura, X. Peng, M. J. Thomas, N. van Doremalen, E. Haddock, L. Nagy, R. LaCasse, T. Liu, J. Zhu, J. S. McLellan, D. P. Scott, M. G. Katze, H. Feldmann, V. J. Munster, Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLOS Pathog. 10, e1004250 (2014).
39. E. de Wit, A. L. Rasmussen, D. Falzarano, T. Bushmaker, F. Feldmann, D. L. Brining, E. R. Fischer, C. Martellaro, A. Okumura, J. Chang, D. Scott, A. G. Benecke, M. G. Katze, H. Feldmann, V. J. Munster, Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc. Natl. Acad. Sci. U.S.A. 110, 16598-16603 (2013).
40. 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-α2β and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 19, 1313-1317 (2013).
41. N. Bennet, Alarm bells over MERS coronavirus. Lancet Infect. Dis. 13, 573-574 (2013).
42. D. Butler, Progress stalled on coronavirus. Nature 501, 294-295 (2013).
43. A. Zumla, D. S. Hui, S. Perlman, Middle East respiratory syndrome. Lancet 10.1016/S0140-6736(15)60454-8 (2015).
44. Z. A. Memish, A. I. Zumla, A. Assiri, Middle East respiratory syndrome coronavirus infections in health care workers. N. Engl. J. Med. 369, 884-886 (2013).
45. Z. A. Memish, A. M. Assiri, J. A. Al-Tawfiq, Middle East respiratory syndrome coronavirus (MERS-CoV) viral shedding in the respiratory tract: An observational analysis with infection control implications. Int. J. Infect. Dis. 29, 307-308 (2014).
46. D. Reinhold, S. Brocke, DPP4-directed therapeutic strategies for MERS-CoV. Lancet Infect. Dis. 14, 100-101 (2014).
47. 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).
48. K. A. Lang Kuhs, R. Toporovski, J. Yan, A. A. Ginsberg, D. J. Shedlock, D. B. Weiner, Induction of intrahepatic HCV NS4B, NS5A and NS5B-specific cellular immune responses following peripheral immunization. PLOS One 7, e52165 (2012).
49. 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).
50. C.-J. Wei, H. M. Yassine, P. M. McTamney, J. G. D. Gall, J. R. R. Whittle, J. C. Boyington, G. J. Nabel, Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure. Sci. Transl. Med. 4, 147ra114 2012).
51. K. Muthumani, M. C. Wise, K. E. Broderick, N. Hutnick, J. Goodman, S. Flingai, J. Yan, C. B. Bian, J. Mendoza, C. Tingey, C. Wilson, K. Wojtak, N. Y. Sardesai, D. B. Weiner, HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B-And T-cell responses and neutralizing phenotype in vivo. PLOS One 8, e84234 (2013).
52. D. J. Shedlock, K. T. Talbott, C. Cress, B. Ferraro, S. Tuyishme, K. Mallilankaraman, N. J. Cisper, M. P. Morrow, S. J. Wu, O. U. Kawalekar, A. S. Khan, N. Y. Sardesai, K. Muthumani, H. Shen, D. B. Weiner, A highly optimized DNA vaccine confers complete protective immunity against high-dose lethal lymphocytic choriomeningitis virus challenge. Vaccine 29, 6755-6762 (2011).
53. A. Frey, J. Di Canzio, D. Zurakowski, A statistically defined endpoint titer determination method for immunoassays. J. Immunol. Methods 221, 35-41 (1998).