Please wait a minute...
Journal of Integrative Agriculture  2017, Vol. 16 Issue (10): 2264-2273    DOI: 10.1016/S2095-3119(17)61660-5
Animal Science · Veterinary Medicine Advanced Online Publication | Current Issue | Archive | Adv Search |
Newcastle disease virus-based MERS-CoV candidate vaccine elicits high-level and lasting neutralizing antibodies in Bactrian camels
Liu Ren-qiang1, Ge Jin-ying1, Wang Jin-ling2, Shao Yu1, Zhang Hui-lei1, Wang Jin-liang1, Wen Zhi-yuan1, Bu Zhi-gao1
1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, P.R.China
2 College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, P.R.China
Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
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  
Received: 17 February 2017   Accepted:
Fund: 

This study was support by National Key Technology R&D Program of China (2013BAD12B05).     

Corresponding Authors:  Correspondence BU Zhi-gao, E-mail: buzhigao@caas.cn; Wen Zhi-yuan, E-mail: zywen7@yahoo.com    
About author:  LIU Ren-qiang, E-mail: lrq29134@163.com

Cite this article: 

Liu Ren-qiang, Ge Jin-ying, Wang Jin-ling, Shao Yu, Zhang Hui-lei, Wang Jin-liang, Wen Zhi-yuan, Bu Zhi-gao . 2017. Newcastle disease virus-based MERS-CoV candidate vaccine elicits high-level and lasting neutralizing antibodies in Bactrian camels. Journal of Integrative Agriculture, 16(10): 2264-2273.

OIE (World Organisation for Animal Health). 2004. OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Office International des Epizooties, Paris.

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, et al. 2013. Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe. Emerging Infectious Diseases, 19, 456–459.

Azhar E I, El-Kafrawy S A, Farraj S A, Hassan A M, Al-Saeed M S, Hashem A M, Madani T A. 2014. Evidence for camel-to-human transmission of MERS coronavirus. The New England Journal of Medicine, 370, 2499–2505.

Belouzard S, Millet J K, Licitra B N, Whittaker G R. 2012. Mechanisms of coronavirus cell entry mediated by the viral spike protein. Viruses, 4, 1011–1033.

Bukreyev A, Collins P L. 2008. Newcastle disease virus as a vaccine vector for humans. Current Opinion in Molecular Therapeutics, 10, 46–55.

Bukreyev A, Skiadopoulos M H, Murphy B R, Collins P L. 2006. Nonsegmented negative-strand viruses as vaccine vectors. Journal of Virology, 80, 10293–10306.

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. 2014. MERS coronaviruses in dromedary camels, Egypt. Emerging Infectious Diseases, 20, 1049–1053.

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. 2010a. 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, 84, 1489–1503.

Di Napoli J M, Yang L, Samal S K, Murphy B R, Collins P L, Bukreyev A. 2010b. Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response. Vaccine, 29, 17–25.

Du L, He Y, Zhou Y, Liu S, Zheng B J, Jiang S. 2009. The spike protein of SARS-CoV - a target for vaccine and therapeutic development. Nature Review Microbiology, 7, 226–236.

Enjuanes L, Dediego M L, Alvarez E, Deming D, Sheahan T, Baric R. 2008. Vaccines to prevent severe acute respiratory syndrome coronavirus-induced disease. Virus Research, 133, 45–62.

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. 2007. 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, 81, 150–158.

Ge J, Tian G, Zeng X, Jiang Y, Chen H, Bua Z. 2010. Generation and evaluation of a Newcastle disease virus-based H9 avian influenza live vaccine. Avian Diseases, 54, 294–296.

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. 2016. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels. Science, 351, 77–81.

Hofmann H, Hattermann K, Marzi A, Gramberg T, Geier M, Krumbiegel M, Kuate S, Uberla K, Niedrig M, Pohlmann S. 2004. 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, 78, 6134–6142.

Khattar S K, Collins P L, Samal S K. 2010. 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, 28, 3159–3170.

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. 2014. Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice. Vaccine, 32, 5975–5982.

Kong D, Wen Z, Su H, Ge J, Chen W, Wang X, Wu C, Yang C, Chen H, Bu Z. 2012. Newcastle disease virus-vectored Nipah encephalitis vaccines induce B and T cell responses in mice and long-lasting neutralizing antibodies in pigs. Virology, 432, 327–335.

Kortekaas J, de Boer S M, Kant J, Vloet R P, Antonis A F, Moormann R J. 2010. Rift Valley fever virus immunity provided by a paramyxovirus vaccine vector. Vaccine, 28, 4394–4401.

Li Z, Jiang Y, Jiao P, Wang A, Zhao F, Tian G, Wang X, Yu K, Bu Z, Chen H. 2006. The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. Journal of Virology, 80, 11115–11123.

Liu R, Wen Z, Wang J, Ge J, Chen H, Bu Z. 2015. 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, 4, e73.

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. 2006. Protection against respiratory syncytial virus by a recombinant Newcastle disease virus vector. Journal of Virology, 80, 1130–1139.

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. 2014. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerging Infectious Diseases, 20, 1012–1015.

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. 2013. Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerging Infectious Diseases, 19, 1819–1823.

Millet J K, Whittaker G R. 2014. 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, 111, 15214–15219.

Modjarrad K, Moorthy V S, Ben Embarek P, Van Kerkhove M, Kim J, Kieny M P. 2016. A roadmap for MERS-CoV research and product development: Report from a World Health Organization consultation. Nature Medicine, 22, 701–705.

Muthumani K, Falzarano D, Reuschel E L, Tingey C, Flingai S, Villarreal D O, Wise M, Patel, A, Izmirly A, Aljuaid A. 2015. A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Science Translational Medicine, 7, 301–132.

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. 2015. 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, 112, 8738–8743.

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. 2013. 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, 18, 20574.

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, et al. 2016. Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia. Science, 351, 81–84.

Song F, Fux R, Provacia L B, Volz A, Eickmann M, Becker S, Osterhaus A D, Haagmans B L, Sutter G. 2013. Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. Journal of Virology, 87, 11950–11954.

Wang C, Zheng X, Gai W, Zhao Y, Wang H, Wang H, Feng N, Chi H, Qiu B, Li N. 2016. MERS-CoV virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques. Oncotarget, 8, 12686–12694.

Wong G, Liu W, Liu Y, Zhou B, Bi Y, Gao G F. 2015. MERS, SARS, and ebola: The role of super-spreaders in infectious disease. Cell Host & Microbe, 18, 398–401.

Wyatt L S, Moss B, Rozenblatt S. 1995. Replication-deficient vaccinia virus encoding bacteriophage T7 RNA polymerase for transient gene expression in mammalian cells. Virology, 210, 202–205.

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, et al. 2016. MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2. Nature Microbiology, 1, 16004.

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. 2016. Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus. Cellular & Molecular Immunology, 13, 180–190.

Zhao J, Li K, Wohlford-Lenane C, Agnihothram S S, Fett C, Zhao J, Gale Jr M J, Baric R S, Enjuanes L, Gallagher T, McCray Jr P B, Perlman S. 2014. Rapid generation of a mouse model for Middle East respiratory syndrome. Proceedings of the National Academy of Sciences of the United States of America, 111, 4970–4975.

Zumla A, Chan J F, Azhar E I, Hui D S, Yuen K Y. 2016. Coronaviruses - Drug discovery and therapeutic options. Nature reviews. Drug Discovery, 15, 327–347.
No related articles found!
No Suggested Reading articles found!