Recombinant Newcastle Disease Virus (NDV) Expressing Sigma C Protein of Avian Reovirus (ARV) Protects against Both ARV and NDV in Chickens

Newcastle disease (ND) and avian reovirus (ARV) infections are a serious threat to the poultry industry, which causes heavy economic losses. The mesogenic NDV strain R2B is commonly used as a booster vaccine in many Asian countries to control the disease. In this seminal work, a recombinant NDV strain R2B expressing the sigma C (σC) gene of ARV (rNDV-R2B-σC) was generated by reverse genetics, characterized in vitro and tested as a bivalent vaccine candidate in chickens. The recombinant rNDV-R2B-σC virus was attenuated as compared to the parent rNDV-R2B virus as revealed by standard pathogenicity assays. The generated vaccine candidate, rNDV-R2B-σC, could induce both humoral and cell mediated immune responses in birds and gave complete protection against virulent NDV and ARV challenges. Post-challenge virus shedding analysis revealed a drastic reduction in NDV shed, as compared to unvaccinated birds.

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A Novel Recombinant Newcastle Disease Virus Vectored DIVA Vaccine against Peste des Petits Ruminants in Goats

Vaccines ◽

10.3390/vaccines8020205 ◽

2020 ◽

Vol 8 (2) ◽

pp. 205 ◽

Cited By ~ 2

Author(s):

Magdalena Murr ◽

Bernd Hoffmann ◽

Christian Grund ◽

Angela Römer-Oberdörfer ◽

Thomas C. Mettenleiter

Keyword(s):

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

Clinical Signs ◽

Surface Protein ◽

Domestic Sheep ◽

Peste Des Petits Ruminants ◽

Virus Shedding ◽

Recombinant Newcastle Disease Virus

Peste des petits ruminants virus (PPRV, species: small ruminant morbillivirus) is the causative agent of the eponymous notifiable disease, the peste des petits ruminants (PPR) in wild and domestic sheep and goats. Mortality rates vary between 50% and 100%, causing significant losses of estimated 1.5 to 2 billion US Dollars per year. Live-attenuated PPRV vaccine strains are used in the field for disease prevention, but the application of a more thermostable vaccine enabling differentiation between infected and vaccinated animals (DIVA) would be highly desirable to achieve the goal of global disease eradication. We generated a recombinant Newcastle disease virus (rNDV) based on the live-attenuated NDV Clone 30 that expresses the surface protein hemagglutinin (H) of PPRV strain Kurdistan/11 (rNDV_HKur). In vitro analyses confirmed transgene expression as well as virus replication in avian, caprine, and ovine cells. Two consecutive subcutaneous vaccinations of German domestic goats with rNDV_HKur prevented clinical signs and hematogenic dissemination after an intranasal challenge with virulent PPRV Kurdistan/11. Virus shedding by different routes was reduced to a similar extent as after vaccination with the live-attenuated PPRV strain Nigeria 75/1. Goats that were either not vaccinated or inoculated with parental rNDV were used as controls. In summary, we demonstrate in a proof-of-concept study that an NDV vectored vaccine can protect against PPR. Furthermore, it provides DIVA-applicability and a high thermal tolerance.

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Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate

10.1101/2021.03.07.434276 ◽

2021 ◽

Author(s):

Manolo Fernandez Díaz ◽

Katherine Calderon ◽

Aldo Rojas-Neyra ◽

Vikram N. Vakharia ◽

Ricardo Choque-Guevara ◽

...

Keyword(s):

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

Vaccine Candidate ◽

Allantoic Fluid ◽

Cellular Damage ◽

Hamster Model ◽

Golden Syrian Hamster ◽

Oncological Treatment

ABSTRACTThe COVID-19 pandemic has claimed the lives of millions of people worldwide and threatens to become an endemic problem, therefore the need for as many types of vaccines as possible is of high importance.Because of the millions of doses required, it is desirable that vaccines are not only safe and effective, but also easy to administer, store, and inexpensive to produce.Newcastle Disease Virus (NDV) is responsible for a respiratory disease in chickens. It has no pathogenic homologue in humans. NDV is recognized as an oncolytic virus, and its use in humans for oncological treatment is being evaluated.In the present work, we have developed two types of NDV-vectored candidate vaccines, which carry the surface-exposed RBD and S1 antigens of SARS-CoV-2, respectively. These vaccine candidates were produced in specific-pathogen-free embryonating chicken eggs, and purified from allantoic fluid before lyophilization. These vaccines were administered intranasally to three different animal models: mice, rats and hamsters, and evaluated for safety, toxicity, immunogenicity, stability and efficacy. Efficacy was evaluated in a challenge assay against active SARS-CoV-2 virus in the Golden Syrian hamster model.The NDV-vectored vaccine based on the S1 antigen was shown to be safe and highly immunogenic, with the ability to neutralize SARS-CoV-2 in-vitro, even with an extreme dilution of 1/640. Our results reveal that this vaccine candidate protects the lungs of the animals, preventing cellular damage in this tissue. In addition, this vaccine reduces the viral load in the lungs, suggesting that it may significantly reduce the likelihood of transmission. Being lyophilized, this vaccine candidate is very stable and can be stored for several months at 4-8⁰C.In conclusion, our NDV-based vaccine candidate has shown a very favorable performance in the pre-clinical study, serving as evidence for a future evaluation in a Phase-I human clinical trial. This candidate represents a promising tool in the fight against COVID-19.

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An improved method for the rescue of recombinant Newcastle disease virus

BioTechniques ◽

10.2144/btn-2019-0110 ◽

2020 ◽

Vol 68 (2) ◽

pp. 96-100

Author(s):

Pheik-Sheen Cheow ◽

Tiong Kit Tan ◽

Adelene Ai-Lian Song ◽

Khatijah Yusoff ◽

Suet Lin Chia

Keyword(s):

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

Reverse Genetics ◽

Vaccine Development ◽

Transfection Efficiency ◽

Transfection Method ◽

Helper Plasmids ◽

Immunogenic Properties ◽

Recombinant Newcastle Disease Virus

Reverse genetics has been used to generate recombinant Newcastle disease virus with enhanced immunogenic properties for vaccine development. The system, which involves co-transfecting the viral antigenomic plasmid with three helper plasmids into a T7 RNA polymerase-expressing cell to produce viral progenies, poses a great challenge. We have modified the standard transfection method to improve the transfection efficiency of the plasmids, resulting in a higher titer of virus progeny production. Two transfection reagents (i.e., lipofectamine and polyethylenimine) were used to compare the transfection efficiency of the four plasmids. The virus progenies produced were quantitated with flow cytometry analysis of the infectious virus unit. The modified transfection method increased the titer of virus progenies compared with that of the standard transfection method.

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Rescue of recombinant Newcastle disease virus: a promising vector with two decades of intensive vaccine research

Future Virology ◽

10.2217/fvl-2019-0063 ◽

2019 ◽

Vol 14 (9) ◽

pp. 617-628 ◽

Cited By ~ 2

Author(s):

Aidin Molouki ◽

Abdou Nagy

Keyword(s):

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

Reverse Genetics ◽

Progeny Virus ◽

Vaccine Research ◽

Human Use ◽

Helper Plasmids ◽

Initiation Sequence ◽

Recombinant Newcastle Disease Virus

Two decades have passed since the first reverse genetics system for the rescue of recombinant Newcastle disease virus was developed. Since then, the recombinant Newcastle disease virus vector has shown promising results as a safe and potent vector for development of many vaccines for both avian and human use. Herein, we review several technical topics that would be useful to further understanding of this technology. First, the effect of using helper plasmids encoding proteins belonging to strains other than the full-length cDNA and the possible incorporation of these expressed proteins into progeny virus will be discussed. Then, we will discuss the effect of removal of additional G residues from the T7 initiation sequence and finally, we will review different ways to improve rescue efficiency.

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Rapid development of SARS-CoV-2 receptor binding domain-conjugated nanoparticle vaccine candidate

10.1101/2020.11.03.366138 ◽

2020 ◽

Author(s):

Yin-Feng Kang ◽

Cong Sun ◽

Zhen Zhuang ◽

Run-Yu Yuan ◽

Qing-Bing Zheng ◽

...

Keyword(s):

Receptor Binding ◽

Vaccine Development ◽

Vaccine Candidate ◽

Rapid Development ◽

Scale Up ◽

Physical Stability ◽

Covalent Bond ◽

Neutralizing Antibody ◽

Economic Losses

AbstractThe ongoing of coronavirus disease 2019 (COVID-19) pandemic caused by novel SARS-CoV-2 coronavirus, resulting in economic losses and seriously threating the human health in worldwide, highlighting the urgent need of a stabilized, easily produced and effective preventive vaccine. The SARS-COV-2 spike protein receptor binding region (RBD) plays an important role in the process of viral binding receptor angiotensin-converting enzyme 2 (ACE2) and membrane fusion, making it an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticles vaccine candidates, RBD-Ferritin (24-mer), RBD-mi3 (60-mer) and RBD-I53-50 (120-mer), with the application of covalent bond linking by SpyTag-SpyCatcher system. It was demonstrated that the neutralizing capability of sera from mice immunized with three RBD-conjugated nanoparticles adjuvanted with AddaVax or Sigma Systerm Adjuvant (SAS) after each immunization was ~8-to 120-fold greater than monomeric RBD group in SARS-CoV-2 pseudovirus and authentic virus neutralization assay. Most importantly, sera from RBD-conjugated NPs groups more efficiently blocked the binding of RBD to ACE2 or neutralizing antibody in vitro, a further proof of promising immunization effect. Besides, high physical stability and flexibility in assembly consolidated the benefit for rapid scale-up production of vaccine. These results supported that our designed SARS-CoV-2 RBD-conjugated nanoparticle was competitive vaccine candidate and the carrier nanoparticles could be adopted as universal platform for future vaccine development.

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Interferon Inducing Porcine Reproductive and Respiratory Syndrome Virus Vaccine Candidate Protected Piglets from HP-PRRSV Challenge and Evoke a Higher Level of Neutralizing Antibodies Response

Vaccines ◽

10.3390/vaccines8030490 ◽

2020 ◽

Vol 8 (3) ◽

pp. 490

Author(s):

Yafei Li ◽

Junhui Li ◽

Sun He ◽

Wei Zhang ◽

Jian Cao ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Respiratory Syndrome Virus ◽

Infection Prevalence ◽

Type I ◽

Lethal Challenge ◽

Virus Shedding ◽

Humoral Immune ◽

Type I Ifns

Although widespread administration of attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccines has been implemented since they first became commercially available two decades ago, PRRSV infection prevalence in swine herds remains high. The limited success of PRRSV vaccines is partly due to the well-established fact that a given vaccine strain confers only partial or no protection against heterologous strains. In our past work, A2MC2-P90, a novel PRRSV vaccine candidate that induced a type I IFNs response in vitro, conferred complete protection against challenge with genetically heterologous PRRSV strains. Here we assessed the ability of the PRRSV vaccine candidate A2MC2-P90 to protect piglets against the HP-PRRSV challenge and compared its efficacy to that of a licensed HP-PRRSV-specific vaccine (TJM-F92) assessed in parallel. A2MC2-P90 provided vaccinated piglets with 100% protection from a lethal challenge with extremely virulent HP-PRRSV-XJA1, while 100% mortality was observed for unvaccinated piglets by day 21 post-challenge. Notably, comparison of partial sequence (GP5) of XJA1 to A2MC2-P90 suggested there was only 88.7% homology. When comparing post-HP-PRRSV challenge responses between piglets administered A2AMC2-P90 versus those immunized with licensed vaccine TJM-F92, A2MC2-P90-vaccinated piglets rapidly developed a stronger protective humoral immune response, as evidenced by much higher titers of neutralizing antibodies, more rapid clearance of viremia and less nasal virus shedding. In conclusion, our data suggest that this novel vaccine candidate A2MC2-P90 has improved protection spectrum against heterologous HP-PRRSV strains.

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In Vitro and In Vivo Metabolomic Profiling after Infection with Virulent Newcastle Disease Virus

Viruses ◽

10.3390/v11100962 ◽

2019 ◽

Vol 11 (10) ◽

pp. 962 ◽

Cited By ~ 1

Author(s):

Panrao Liu ◽

Yuncong Yin ◽

Yabin Gong ◽

Xusheng Qiu ◽

Yingjie Sun ◽

...

Keyword(s):

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

High Performance ◽

Economic Losses ◽

Viral Protein Synthesis ◽

Metabolomic Profiling ◽

Virulent Newcastle Disease Virus

Newcastle disease (ND) is an acute, febrile, highly contagious disease caused by the virulent Newcastle disease virus (vNDV). The disease causes serious economic losses to the poultry industry. However, the metabolic changes caused by vNDV infection remain unclear. The objective of this study was to determine the metabolomic profiling after infection with vNDV. DF-1 cells infected with the vNDV strain Herts/33 and the lungs from Herts/33-infected specific pathogen-free (SPF) chickens were analyzed via ultra-high-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) in combination with multivariate statistical analysis. A total of 305 metabolites were found to have changed significantly after Herts/33 infection, and most of them belong to the amino acid and nucleotide metabolic pathway. It is suggested that the increased pools of amino acids and nucleotides may benefit viral protein synthesis and genome amplification to promote NDV infection. Similar results were also confirmed in vivo. Identification of these metabolites will provide information to further understand the mechanism of vNDV replication and pathogenesis.

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