Development of a novel thermostable Newcastle disease virus vaccine vector for expression of a heterologous gene

Wen, Guoyuan; Chen, Chen; Guo, Jing; Zhang, Zhenyu; Shang, Yu; Shao, Hongxia; Luo, Qing; Yang, Jun; Wang, Hongling; Wang, Hongcai; Zhāng, Téngfēi; Zhang, Rongrong; Cheng, Guofu; Yu, Qingzhong

doi:10.1099/vir.0.000067

Cited by 35 publications

(38 citation statements)

References 39 publications

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“…In addition to the "conventional model" for foreign gene expression through an additional independent transcription unit (ITU), different approaches for expression of a foreign gene by NDV have been explored (Wen et al, 2015) (Gao et al, 2008). Some of them increased the capacity of expressing a larger gene or more than one foreign gene.…”

Section: Ndv-vectored Vaccinesmentioning

confidence: 99%

Newcastle disease vaccines—A solved problem or a continuous challenge?

Dimitrov

Afonso

et al. 2017

Veterinary Microbiology

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Newcastle disease (ND) has been defined by the World Organisation for Animal Health as infection of poultry with virulent strains of Newcastle disease virus (NDV). Lesions affecting the neurological, gastrointestinal, respiratory, and reproductive systems are most often observed. The control of ND must include strict biosecurity that prevents virulent NDV from contacting poultry, and also proper administration of efficacious vaccines. When administered correctly to healthy birds, ND vaccines formulated with NDV of low virulence or viral-vectored vaccines that express the NDV fusion protein are able to prevent clinical disease and mortality in chickens upon infection with virulent NDV. Live and inactivated vaccines have been widely used since the 1950's. Recombinant and antigenically matched vaccines have been adopted recently in some countries, and many other vaccine approaches have been only evaluated experimentally. Despite decades of research and development towards formulation of an optimal ND vaccine, improvements are still needed. Impediments to prevent outbreaks include uneven vaccine application when using mass administration techniques in larger commercial settings, the difficulties associated with vaccinating free-roaming, multi-age birds of village flocks, and difficulties maintaining the cold chain to preserve the thermo-labile antigens in the vaccines. Incomplete or improper immunization often results in the disease and death of poultry after infection with virulent NDV. Another cause of decreased vaccine efficacy is the existence of antibodies (including maternal) in birds, which can neutralize the vaccine and thereby reduce the effectiveness of ND vaccines. In this review, a historical perspective, summary of the current situation for ND and NDV strains, and a review of traditional and experimental ND vaccines are presented.

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Section: Ndv-vectored Vaccinesmentioning

confidence: 99%

Newcastle disease vaccines—A solved problem or a continuous challenge?

Dimitrov

Afonso

et al. 2017

Veterinary Microbiology

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294

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“…Fertile white leghorn SPF embryonated eggs were purchased from the Beijing Merial Vital Laboratory Animal Technology Co., Ltd. The recombinant avirulent NDV LaSota strain was developed previously in our laboratory by a reverse genetics system [35,36]. The velogenic NDV genotype IX strain F48E9 [37] and Massachusetts IBV strain M41 obtained from the China Institute of Veterinary Drug Control (Beijing, China) were stored in our laboratory at -70 • C. The 50% embryo infectious dose (EID 50 ) of a virus in harvested allantoic fluid was calculated by the Reed and Muench mathematical technique [38].…”

Section: Cells Viruses and Ethics Statementmentioning

confidence: 99%

A Recombinant La Sota Vaccine Strain Expressing Multiple Epitopes of Infectious Bronchitis Virus (IBV) Protects Specific Pathogen-Free (SPF) Chickens against IBV and NDV Challenges

et al. 2019

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Infectious bronchitis (IB) and Newcastle disease (ND) are two major infectious diseases that are a threat to the domestic poultry industry. In this study, we successfully generated a recombinant LaSota candidate vaccine strain, rNDV-IBV-T/B, which expresses a short, synthetic, previously identified IBV S1 multi-epitope cassette using the reverse genetic system. The recombinant virus was propagated in nine-day-old embryonated chicken eggs for 20 passages and genetic stability was confirmed by whole genome DNA sequencing. The recombinant virus had a hemagglutination (HA) titer of 2 10 , mean death time (MDT) of 118 hours, and intracerebral pathogenicity index (ICPI) of 0.05. None of these were significantly different from the parental Newcastle disease virus (NDV) LaSota strain (p > 0.05). Vaccination of white leghorn chickens at one day of age with 10 6 EID 50 rNDV-IBV-T/B provided 90% protection against virulent IBV M41 challenge at three weeks of age, which was significantly higher than the protection of the control group vaccinated with phosphate-buffered saline (PBS) (p < 0.05). The ciliostasis scores of rNDV-IBV-T/B-vaccinated and LaSota-vaccinated groups were 4.2 and 37.6, respectively, which indicated that rNDV-IBV-T/B vaccination reduced the pathogenicity of IBV toward the trachea. Furthermore, real-time RT-PCR assay showed that the rNDV-IBV-T/B vaccination resulted in low levels of viral load (647.80 ± 49.65 RNA copies) in the trachea four days post-challenge, which is significantly lower than groups vaccinated with PBS (8591.25 ± 311.10 RNA copies) or LaSota (7742.60 ± 298.50 RNA copies) (p < 0.05). Meanwhile, the same dose of rNDV-IBV-T/B vaccination provided complete protection against velogenic NDV F48E9 challenge. These results demonstrate that the rNDV-IBV-T/B strain is a promising vaccine candidate to control both IB and ND simultaneously. Furthermore, epitope-based live vector vaccines provide an alternative strategy for the development of cost-effective and, broadly, cross-protective vaccines.

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“…However, there is concern about the stability of the engineered segmented NDV because the majority of infectious NDV particles contain a single genome (Goff et al, 2012). In 2015, Wen et al (2015) developed a new approach to express a foreign gene by NDV as a fusion protein with the M protein, followed by self-cleavage of foot-and-mouth disease 2A peptide and ubiquitin coding sequences. After cleavage, the foreign protein contains an extra 20 aa at the amino-terminus and 17 aa at the carboxyl-terminus derived from the M protein of NDV and the 2A peptide and ubiquitin, respectively.…”

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confidence: 99%

Development of a Newcastle disease virus vector expressing a foreign gene through an internal ribosomal entry site provides direct proof for a sequential transcription mechanism

Zhang

Zhao

et al. 2015

Journal of General Virology

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In the present study, we developed a novel approach for foreign gene expression by Newcastle disease virus (NDV) from a second ORF through an internal ribosomal entry site (IRES). Six NDV LaSota strain-based recombinant viruses vectoring the IRES and a red fluorescence protein (RFP) gene behind the nucleocapsid (NP), phosphoprotein (P), matrix (M), fusion (F), haemagglutinin-neuraminidase (HN) or large polymerase (L) gene ORF were generated using reverse genetics technology. The insertion of the second ORF slightly attenuated virus pathogenicity, but did not affect ability of the virus to grow. Quantitative measurements of RFP expression in virus-infected DF-1 cells revealed that the abundance of viral mRNAs and red fluorescence intensity were positively correlated with the gene order of NDV, 39-NP-P-M-F-HN-L-59, proving the sequential transcription mechanism for NDV. The results herein suggest that the level of foreign gene expression could be regulated by selecting the second ORF insertion site to maximize the efficacy of vaccine and gene therapy. Newcastle disease virus (NDV) is a member of the genus Avulavirus within the subfamily Paramyxovirinae of the family Paramyxoviridae (Lamb et al., 2005). The genome of NDV is a non-segmented, negative-sense ssRNA of 15.2 kb that contains six genes, in the order 39-nucleocapsid (NP)-phosphoprotein (P)-matrix (M)-fusion (F)-haemagglutininneuraminidase (HN)-large polymerase (L)-59, flanked by a 39 UTR leader and 59 trailer Peeters et al., 2000). Two additional proteins (V and W) are produced through editing of the phosphoprotein mRNA (Steward et al., 1993). The genomic RNA is encapsidated with the NP protein and associated with the P and L proteins to form the ribonucleoprotein complex (RNP), which is an active template for viral RNA transcription and replication . Based on their pathogenicity for chickens, NDV strains have been classified into lentogenic (low virulence), mesogenic (intermediate virulence) and velogenic (high virulence) pathotypes (Miller & Koch, 2013). Virulent strains of NDV are the causative agents of Newcastle disease (ND), affecting a wide variety of birds and causing significant economic losses to the poultry industry worldwide (Alexander, 2001). Some lentogenic NDV strains, such as LaSota and B1, have been used as vaccines to protect poultry against ND worldwide.During the late 1990s, reverse genetics technology was developed to rescue infectious NDV from cloned cDNAs Römer-Oberdörfer et al., 1999). Since then, many strains of NDV have been developed as vectors to express foreign genes for vaccine or gene therapy purposes Bukreyev et al., 2005;DiNapoli et al., 2007DiNapoli et al., , 2010 Ge et al., 2007Ge et al., , 2010Hu et al., 2011;Kong et al., 2012; Kortekaas et al., 2010;Niu et al., 2014;Yu et al., 2013;Zhao & Peeters, 2003;Zhao et al., 2014). Usually, the foreign genes are inserted into a non-coding region in the NDV genome as an additional independent transcription unit (ITU) that consists of NDV gene start, the foreign gene and NDV gene...

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Development of a novel thermostable Newcastle disease virus vaccine vector for expression of a heterologous gene

Cited by 35 publications

References 39 publications

Newcastle disease vaccines—A solved problem or a continuous challenge?

Newcastle disease vaccines—A solved problem or a continuous challenge?

A Recombinant La Sota Vaccine Strain Expressing Multiple Epitopes of Infectious Bronchitis Virus (IBV) Protects Specific Pathogen-Free (SPF) Chickens against IBV and NDV Challenges

Development of a Newcastle disease virus vector expressing a foreign gene through an internal ribosomal entry site provides direct proof for a sequential transcription mechanism

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