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. 2017 Oct 9;16(10):2264–2273. doi: 10.1016/S2095-3119(17)61660-5

Newcastle disease virus-based MERS-CoV candidate vaccine elicits high-level and lasting neutralizing antibodies in Bactrian camels

Ren-qiang LIU a, Jin-ying GE a, Jin-ling WANG b, Yu SHAO a, Hui-lei ZHANG a, Jin-liang WANG a, Zhi-yuan WEN a, Zhi-gao BU a,*
PMCID: PMC7128255  PMID: 32288953

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV), a member of the Coronaviridae family, is the causative pathogen for MERS that is characterized by high fever, pneumonia, acute respiratory distress syndrome (ARDS), as well as extrapulmonary manifestations. Currently, there are no approved treatment regimens or vaccines for MERS. Here, we generated recombinant nonvirulent Newcastle disease virus (NDV) LaSota strain expressing MERS-CoV S protein (designated as rLa-MERS-S), and evaluated its immunogenicity in mice and Bactrian camels. The results revealed that rLa-MERS-S showed similar growth properties to those of LaSota in embryonated chicken eggs, while animal immunization studies showed that rLa-MERS-S induced MERS-CoV neutralizing antibodies in mice and camels. Our findings suggest that recombinant rLa-MERS-S may be a potential MERS-CoV veterinary vaccine candidate for camels and other animals affected by MERS.

Keywords: Newcastle disease virus, MERS-CoV, neutralizing antibodies, camels

Contributor Information

Ren-qiang LIU, Email: lrq29134@163.com.

Zhi-yuan WEN, Email: zywen7@yahoo.com.

Zhi-gao BU, Email: buzhigao@caas.cn.

References

  1. OIE (World Organisation for Animal Health) OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Office International des Epizooties; Paris: 2004. [Google Scholar]
  2. Annan A, Baldwin H J, Corman V M, Klose S M, Owusu M, Nkrumah E E, Badu E K, Anti P, Agbenyega O, Meyer B, Oppong S, Sarkodie Y A, Kalko E K, Lina P H, Godlevska E V, Reusken C, Seebens A, Gloza-Rausch F, Vallo P, Tschapka M. Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe. Emerging Infectious Diseases. 2013;19:456–459. doi: 10.3201/eid1903.121503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Azhar E I, El-Kafrawy S A, Farraj S A, Hassan A M, Al-Saeed M S, Hashem A M, Madani T A. Evidence for camel-to-human transmission of MERS coronavirus. The New England Journal of Medicine. 2014;370:2499–2505. doi: 10.1056/NEJMoa1401505. [DOI] [PubMed] [Google Scholar]
  4. Belouzard S, Millet J K, Licitra B N, Whittaker G R. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses. 2012;4:1011–1033. doi: 10.3390/v4061011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bukreyev A, Collins P L. Newcastle disease virus as a vaccine vector for humans. Current Opinion in Molecular Therapeutics. 2008;10:46–55. [PubMed] [Google Scholar]
  6. Bukreyev A, Skiadopoulos M H, Murphy B R, Collins P L. Nonsegmented negative-strand viruses as vaccine vectors. Journal of Virology. 2006;80:10293–10306. doi: 10.1128/JVI.00919-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chu D K, Poon L L, Gomaa M M, Shehata M M, Perera R A, Abu Zeid D, El Rifay A S, Siu L Y, Guan Y, Webby R J, Ali M A, Peiris M, Kayali G. MERS coronaviruses in dromedary camels, Egypt. Emerging Infectious Diseases. 2014;20:1049–1053. doi: 10.3201/eid2006.140299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Di Napoli J M, Nayak B, Yang L, Finneyfrock B W, Cook A, Andersen H, Torres-Velez F, Murphy B R, Samal S K, Collins P L, Bukreyev A. Newcastle disease virus-vectored vaccines expressing the hemagglutinin or neuraminidase protein of H5N1 highly pathogenic avian influenza virus protect against virus challenge in monkeys. Journal of Virology. 2010;84:1489–1503. doi: 10.1128/JVI.01946-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Di Napoli J M, Yang L, Samal S K, Murphy B R, Collins P L, Bukreyev A. Respiratory tract immunization of nonhuman primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response. Vaccine. 2010;29:17–25. doi: 10.1016/j.vaccine.2010.10.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Du L, He Y, Zhou Y, Liu S, Zheng B J, Jiang S. The spike protein of SARS-CoV – A target for vaccine and therapeutic development. Nature Review Microbiology. 2009;7:226–236. doi: 10.1038/nrmicro2090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Enjuanes L, Dediego M L, Alvarez E, Deming D, Sheahan T, Baric R. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease. Virus Research. 2008;133:45–62. doi: 10.1016/j.virusres.2007.01.021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ge J, Deng G, Wen Z, Tian G, Wang Y, Shi J, Wang X, Li Y, Hu S, Jiang Y, Yang C, Yu K, Bu Z, Chen H. Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. Journal of Virology. 2007;81:150–158. doi: 10.1128/JVI.01514-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ge J, Tian G, Zeng X, Jiang Y, Chen H, Bua Z. Generation and evaluation of a Newcastle disease virus-based H9 avian influenza live vaccine. Avian Diseases. 2010;54:294–296. doi: 10.1637/8731-032509-ResNote.1. [DOI] [PubMed] [Google Scholar]
  14. Haagmans B L, van den Brand J M, Raj V S, Volz A, Wohlsein P, Smits S L, Schipper D, Bestebroer T M, Okba N, Fux R, Bensaid A, Solanes Foz D, Kuiken T, Baumgartner W, Segales J, Sutter G, Osterhaus A D. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science. 2016;351:77–81. doi: 10.1126/science.aad1283. [DOI] [PubMed] [Google Scholar]
  15. Hofmann H, Hattermann K, Marzi A, Gramberg T, Geier M, Krumbiegel M, Kuate S, Uberla K, Niedrig M, Pohlmann S. S protein of severe acute respiratory syndrome-associated coronavirus mediates entry into hepatoma cell lines and is targeted by neutralizing antibodies in infected patients. Journal of Virology. 2004;78:6134–6142. doi: 10.1128/JVI.78.12.6134-6142.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Khattar S K, Collins P L, Samal S K. Immunization of cattle with recombinant Newcastle disease virus expressing bovine herpesvirus-1 (BHV-1) glycoprotein D induces mucosal and serum antibody responses and provides partial protection against BHV-1. Vaccine. 2010;28:3159–3170. doi: 10.1016/j.vaccine.2010.02.051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kim E, Okada K, Kenniston T, Raj V S, AlHajri M M, Farag E A, AlHajri F, Osterhaus A D, Haagmans B L, Gambotto A. Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice. Vaccine. 2014;32:5975–5982. doi: 10.1016/j.vaccine.2014.08.058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kong D, Wen Z, Su H, Ge J, Chen W, Wang X, Wu C, Yang C, Chen H, Bu Z. Newcastle disease virus-vectored Nipah encephalitis vaccines induce B and T cell responses in mice and long-lasting neutralizing antibodies in pigs. Virology. 2012;432:327–335. doi: 10.1016/j.virol.2012.06.001. [DOI] [PubMed] [Google Scholar]
  19. Kortekaas J, de Boer S M, Kant J, Vloet R P, Antonis A F, Moormann R J. Rift Valley fever virus immunity provided by a paramyxovirus vaccine vector. Vaccine. 2010;28:4394–4401. doi: 10.1016/j.vaccine.2010.04.048. [DOI] [PubMed] [Google Scholar]
  20. Li Z, Jiang Y, Jiao P, Wang A, Zhao F, Tian G, Wang X, Yu K, Bu Z, Chen H. The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. Journal of Virology. 2006;80:11115–11123. doi: 10.1128/JVI.00993-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Liu R, Wen Z, Wang J, Ge J, Chen H, Bu Z. Absence of Middle East respiratory syndrome coronavirus in Bactrian camels in the West Inner Mongolia Autonomous Region of China: Surveillance study results from July 2015. Emerging Microbes & Infections. 2015;4:e73. doi: 10.1038/emi.2015.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Martinez-Sobrido L, Gitiban N, Fernandez-Sesma A, Cros J, Mertz S E, Jewell N A, Hammond S, Flano E, Durbin R K, Garcia-Sastre A, Durbin J E. Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector. Journal of Virology. 2006;80:1130–1139. doi: 10.1128/JVI.80.3.1130-1139.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Memish Z A, Cotten M, Meyer B, Watson S J, Alsahafi A J, Al Rabeeah A A, Corman V M, Sieberg A, Makhdoom H Q, Assiri A, Al Masri M, Aldabbagh S, Bosch B J, Beer M, Muller M A, Kellam P, Drosten C. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerging Infectious Diseases. 2014;20:1012–1015. doi: 10.3201/eid2006.140402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Memish Z A, Mishra N, Olival K J, Fagbo S F, Kapoor V, Epstein J H, Alhakeem R, Durosinloun A, Al Asmari M, Islam A, Kapoor A, Briese T, Daszak P, Al Rabeeah A A, Lipkin W I. Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerging Infectious Diseases. 2013;19:1819–1823. doi: 10.3201/eid1911.131172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Millet J K, Whittaker G R. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein. Proceedings of the National Academy of Sciences of the United States of America. 2014;111:15214–15219. doi: 10.1073/pnas.1407087111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Modjarrad K, Moorthy V S, Ben Embarek P, Van Kerkhove M, Kim J, Kieny M P. A roadmap for MERS-CoV research and product development: Report from a World Health Organization consultation. Nature Medicine. 2016;22:701–705. doi: 10.1038/nm.4131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Muthumani K, Falzarano D, Reuschel E L, Tingey C, Flingai S, Villarreal D O, Wise M, Patel A, Izmirly A, Aljuaid A. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Science Translational Medicine. 2015;7:301–312. doi: 10.1126/scitranslmed.aac7462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pascal K E, Coleman C M, Mujica A O, Kamat V, Badithe A, Fairhurst J, Hunt C, Strein J, Berrebi A, Sisk J M, Matthews K L, Babb R, Chen G, Lai K M, Huang T T, Olson W, Yancopoulos G D, Stahl N, Frieman M B, Kyratsous C A. Pre- and postexposure efficacy of fully human antibodies against Spike protein in a novel humanized mouse model of MERS-CoV infection. Proceedings of the National Academy of Sciences of the United States of America. 2015;112:8738–8743. doi: 10.1073/pnas.1510830112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Perera R A, Wang P, Gomaa M R, El-Shesheny R, Kandeil A, Bagato O, Siu L Y, Shehata M M, Kayed A S, Moatasim Y, Li M, Poon L L, Guan Y, Webby R J, Ali M A, Peiris J S, Kayali G. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Eurosurveillance. 2013;18:20574. doi: 10.2807/1560-7917.es2013.18.36.20574. [DOI] [PubMed] [Google Scholar]
  30. Sabir J S, Lam T T, Ahmed M M, Li L, Shen Y, Abo-Aba S E, Qureshi M I, Abu-Zeid M, Zhang Y, Khiyami M A, Alharbi N S, Hajrah N H, Sabir M J, Mutwakil M H, Kabli S A, Alsulaimany F A, Obaid A Y, Zhou B, Smith D K, Holmes E C. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science. 2016;351:81–84. doi: 10.1126/science.aac8608. [DOI] [PubMed] [Google Scholar]
  31. Song F, Fux R, Provacia L B, Volz A, Eickmann M, Becker S, Osterhaus A D, Haagmans B L, Sutter G. Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. Journal of Virology. 2013;87:11950–11954. doi: 10.1128/JVI.01672-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wang C, Zheng X, Gai W, Zhao Y, Wang H, Wang H, Feng N, Chi H, Qiu B, Li N. MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques. Oncotarget. 2016;8:12686–12694. doi: 10.18632/oncotarget.8475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wong G, Liu W, Liu Y, Zhou B, Bi Y, Gao G F. MERS, SARS, and ebola: The role of super-spreaders in infectious disease. Cell Host & Microbe. 2015;18:398–401. doi: 10.1016/j.chom.2015.09.013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wyatt L S, Moss B, Rozenblatt S. Replication-deficient vaccinia virus encoding bacteriophage T7 RNA polymerase for transient gene expression in mammalian cells. Virology. 1995;210:202–205. doi: 10.1006/viro.1995.1332. [DOI] [PubMed] [Google Scholar]
  35. Yeung M L, Yao Y, Jia L, Chan J F, Chan K H, Cheung K F, Chen H, Poon V K, Tsang A K, To K K, Yiu M K, Teng J L, Chu H, Zhou J, Zhang Q, Deng W, Lau S K, Lau J Y, Woo P C, Chan T M. MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2. Nature Microbiology. 2016;1:16004. doi: 10.1038/nmicrobiol.2016.4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zhang N, Channappanavar R, Ma C, Wang L, Tang J, Garron T, Tao X, Tasneem S, Lu L, Tseng C T, Zhou Y, Perlman S, Jiang S, Du L. Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus. Cellular & Molecular Immunology. 2016;13:180–190. doi: 10.1038/cmi.2015.03. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Zhao J, Li K, Wohlford-Lenane C, Agnihothram S S, Fett C, Zhao J, Gale M J, Jr, Baric R S, Enjuanes L, Gallagher T, McCray P B, Jr, Perlman S. Rapid generation of a mouse model for Middle East respiratory syndrome. Proceedings of the National Academy of Sciences of the United States of America. 2014;111:4970–4975. doi: 10.1073/pnas.1323279111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zumla A, Chan J F, Azhar E I, Hui D S, Yuen K Y. Coronaviruses – Drug discovery and therapeutic options. Nature reviews. Drug Discovery. 2016;15:327–347. doi: 10.1038/nrd.2015.37. [DOI] [PMC free article] [PubMed] [Google Scholar]

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