Potential as an aerosol vaccine of an improved Newcastle disease vaccine derived from the LaSota strain—II. In vivo studies

Background This study determined whether the naturally attenuated, thermotolerant Newcastle disease vaccine virus I-2 could acquire virulence after five in vivo passages through SPF chickens. Methods Study design was to international requirements including European Pharmacopoeia, Ph. Eur., v9.0 04/2013:0450, 2013. I-2 Working Seed (WS) was compared with five-times-passaged I-2 WS (5XP WS) in intracerebral pathogenicity index (ICPI), Fo cleavage site sequencing and Safety tests. Results The first passage series used a 50% brain: 50% tracheal tissue challenge homogenate and was unsuccessful as I-2 was not detected after the fourth passage. A second passage series used 10% brain: 90% tracheal tissue homogenates. I-2 was isolated from tracheal tissue in each passage. However harvested titres were below the minimum challenge level (107 EID50) specified for the ICPI and Safety tests, possibly reflecting I-2’s inherently low pathogenicity (interestingly caecal tonsils yielded significant titres). Given this the WS and 5XP WS comparisons proceeded. ICPI values were 0.104 and 0.073 for the WS group and the 5XP WS group respectively confirming that I-2, whether passaged or not, expressed low pathogenicity. F0 amino-acid sequences for both WS and 5XP WS were identified as 112R-K-Q-G-R-↓-L-I-G119 and so compatible with those of avirulent ND viruses. In safety, no abnormal clinical signs were observed in both groups except for two chicks in the 5XP WS group, where one bird was withdrawn due to a vent prolapse, and another bird died with inconclusive necropsy results. Conclusions: These data, the issue of low passage titres with little or no virus isolation from brain tissues and the genomic copy approach suggest a need to amend Ph. Eur. v9.0 04/2013:0450, 2013 for naturally attenuated, low pathogenicity vaccine viruses such as I-2. From an international regulatory perspective, the study provides further definitive data demonstrating that Newcastle disease vaccine virus I-2 is safe for use.

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Enhancement of mucosal immune responses by intranasal co-delivery of Newcastle disease vaccine plus CpG oligonucleotide in SPF chickens in vivo

Research in Veterinary Science ◽

10.1016/j.rvsc.2008.02.006 ◽

2008 ◽

Vol 85 (3) ◽

pp. 495-502 ◽

Cited By ~ 23

Author(s):

Linghua Zhang ◽

Meirong Zhang ◽

Jiaoqing Li ◽

Ting Cao ◽

Xingshan Tian ◽

...

Keyword(s):

Immune Responses ◽

Newcastle Disease ◽

Cpg Oligonucleotide ◽

Mucosal Immune Responses ◽

Newcastle Disease Vaccine

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Newcastle disease vaccine virus I-2 fails to acquire virulence during repeated passage in vivo

Gates Open Research ◽

10.12688/gatesopenres.13212.1 ◽

2021 ◽

Vol 5 ◽

pp. 76

Author(s):

Shahn P.R. Bisschop ◽

Andrew Peters ◽

Gil Domingue ◽

Michael C. Pearce ◽

Jeanette Verwey ◽

...

Keyword(s):

Newcastle Disease ◽

Clinical Signs ◽

Vaccine Virus ◽

Amino Acid Sequences ◽

Tissue Homogenates ◽

Tracheal Tissue ◽

Repeated Passage ◽

Low Passage ◽

Newcastle Disease Vaccine

Background This study determined whether the naturally attenuated, thermotolerant Newcastle disease vaccine virus I-2 could acquire virulence after five in vivo passages through SPF chickens. Methods Study design was to international requirements including European Pharmacopoeia, Ph. Eur., v9.0 04/2013:0450, 2013. I-2 Working Seed (WS) was compared with five-times-passaged I-2 WS (5XP WS) in intracerebral pathogenicity index (ICPI), Fo cleavage site sequencing and Safety tests. Results The first passage series used a 50% brain: 50% tracheal tissue challenge homogenate and was unsuccessful as I-2 was not detected after the fourth passage. A second passage series used 10% brain: 90% tracheal tissue homogenates. I-2 was isolated from tracheal tissue in each passage. However harvested titres were below the minimum challenge level (107 EID50) specified for the ICPI and Safety tests, possibly reflecting I-2’s inherently low pathogenicity (interestingly caecal tonsils yielded significant titres). Given this the WS and 5XP WS comparisons proceeded. ICPI values were 0.104 and 0.073 for the WS group and the 5XP WS group respectively confirming that I-2, whether passaged or not, expressed low pathogenicity. F0 amino-acid sequences for both WS and 5XP WS were identified as 112R-K-Q-G-R-↓-L-I-G119 and so compatible with those of avirulent ND viruses. In safety, no abnormal clinical signs were observed in both groups except for two chicks in the 5XP WS group, where one bird was withdrawn due to a vent prolapse, and another bird died with inconclusive necropsy results. Conclusions: These data, the issue of low passage titres with little or no virus isolation from brain tissues and the genomic copy approach suggest a need to amend Ph. Eur. v9.0 04/2013:0450, 2013 for naturally attenuated, low pathogenicity vaccine viruses such as I-2. These results add to the literature and field data demonstrating that Newcastle Disease vaccine virus I-2 is safe for use.

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Newcastle disease vaccine virus I-2 fails to acquire virulence during repeated passage in vivo

Gates Open Research ◽

10.12688/gatesopenres.13212.3 ◽

2021 ◽

Vol 5 ◽

pp. 76

Author(s):

Shahn P.R. Bisschop ◽

Andrew Peters ◽

Gil Domingue ◽

Michael C. Pearce ◽

Jeanette Verwey ◽

...

Keyword(s):

Newcastle Disease ◽

Clinical Signs ◽

Vaccine Virus ◽

Amino Acid Sequences ◽

Tissue Homogenates ◽

Tracheal Tissue ◽

Repeated Passage ◽

Low Passage ◽

Newcastle Disease Vaccine

Background This study determined whether the naturally attenuated, thermotolerant Newcastle disease vaccine virus I-2 could acquire virulence after five in vivo passages through SPF chickens. Methods Study design was to international requirements including European Pharmacopoeia, Ph. Eur., v9.0 04/2013:0450, 2013. I-2 Working Seed (WS) was compared with five-times-passaged I-2 WS (5XP WS) in intracerebral pathogenicity index (ICPI), Fo cleavage site sequencing and Safety tests. Results The first passage series used a 50% brain: 50% tracheal tissue challenge homogenate and was unsuccessful as I-2 was not detected after the fourth passage. A second passage series used 10% brain: 90% tracheal tissue homogenates. I-2 was isolated from tracheal tissue in each passage. However harvested titres were below the minimum challenge level (107 EID50) specified for the ICPI and Safety tests, possibly reflecting I-2’s inherently low pathogenicity (interestingly caecal tonsils yielded significant titres). Given this the WS and 5XP WS comparisons proceeded. ICPI values were 0.104 and 0.073 for the WS group and the 5XP WS group respectively confirming that I-2, whether passaged or not, expressed low pathogenicity. F0 amino-acid sequences for both WS and 5XP WS were identified as 112R-K-Q-G-R-↓-L-I-G119 and so compatible with those of avirulent ND viruses. In safety, no abnormal clinical signs were observed in both groups except for two chicks in the 5XP WS group, where one bird was withdrawn due to a vent prolapse, and another bird died with inconclusive necropsy results. Conclusions: These data, the issue of low passage titres with little or no virus isolation from brain tissues and the genomic copy approach suggest a need to amend Ph. Eur. v9.0 04/2013:0450, 2013 for naturally attenuated, low pathogenicity vaccine viruses such as I-2. From an international regulatory perspective, the study provides further definitive data demonstrating that Newcastle disease vaccine virus I-2 is safe for use.

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In vivo Studies of Antivival Effect of Tetrapleura tetraptera Extracts on Newcastle Disease Virus

Journal of Advances in Microbiology ◽

10.9734/jamb/2017/34521 ◽

2017 ◽

Vol 4 (3) ◽

pp. 1-8

Author(s):

G Ezeifeka ◽

P Nwiyi ◽

C Azuonye ◽

I Erumaka ◽

A Onyeabor ◽

...

Keyword(s):

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

In Vivo Studies ◽

Tetrapleura Tetraptera

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Antiviral activity of Curcuma longa against Newcastle disease virus (in vitro and in vivo studies)

Journal of Veterinary Medical Research ◽

10.21608/jvmr.2020.77624 ◽

2010 ◽

Vol 20 (1) ◽

pp. 290-295

Author(s):

S. M. Tamam ◽

H. M. Madbouly ◽

Fadwa Amin

Keyword(s):

Antiviral Activity ◽

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

Curcuma Longa ◽

In Vivo Studies

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Bioluminescence evaluation of efficacy of oncolytic treatment with Newcastle disease virus (NDV) in malignant pleural mesothelioma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e14536 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e14536-e14536

Author(s):

G. Silberhumer ◽

P. Brader ◽

J. Wong ◽

D. Zamarin ◽

I. Serganova ◽

...

Keyword(s):

Newcastle Disease Virus ◽

Cell Lines ◽

Malignant Pleural Mesothelioma ◽

Newcastle Disease ◽

Bioluminescence Imaging ◽

In Vivo Studies ◽

Pleural Mesothelioma ◽

Viral Therapy ◽

Mesothelioma Cell

e14536 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from multipotent cells of the pleura. Chemotherapy and radiation have very limited therapeutic effects, and average survival time after diagnosis varies between 10 and 16 months. Immunotherapy, gene therapy (oncolytic viral therapy), and photodynamic therapy offer alternative treatment options, with promising results in animal studies. In the following study, the oncolytic efficacy of Newcastle disease virus (NDV(F3aa)-GFP) on MPM is tested and investigated by bioluminescence imaging. Methods: NDV(F3aa)-GFP was tested for viral cytotoxicity at different multiplicities of infection (MOI) against several mesothelioma cell lines in vitro by analyzing release of intracellular lactate dehydrogenase. For in vivo studies, MSTO 211H cells were transduced with firefly (Photinus pyralis) luciferase (FLuc)- encoding cDNAs (MSTO td 211H). Tumor-bearing animals (1e7 cells injected intrapleurally) were treated with either single or multiple doses of NDV(F3aa)-GFP (1e7 plaque-forming units) at different time points (days 1, 3, and 10) and followed by bioluminescence imaging. Results: Mesothelioma cell lines exhibited susceptibility to NDV lysis in the following order of sensitivity: MSTO 211H>MSTO td 211H>H-2452>VAMT>JMN. The cell lines H-2052, H-2373, and HMESO were not sensitive to viral treatment. In vivo studies with MSTO td 211H cells showed complete response to viral therapy in >75% of the animals, resulting in eradication of tumor detected by bioluminescence imaging at day 10 after treatment. Control animals were sacrificed after 23 days due to tumor burden, while >72% of the virally treated animals survived >50 days after tumor injection. No signs of toxicity were observed in the treatment group. In addition, multiple treatment showed a significantly better response compared with single treatment (p=0.005). Conclusions: NDV appears to be an efficient viral oncolytic agent in therapy of malignant pleural mesothelioma in a murine model, and warrants further investigation as a potential therapeutic agent. No significant financial relationships to disclose.

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The oncolytic Newcastle disease virus as an effective immunotherapeutic strategy against glioblastoma

Neurosurgical FOCUS ◽

10.3171/2020.11.focus20842 ◽

2021 ◽

Vol 50 (2) ◽

pp. E8

Author(s):

Joshua A. Cuoco ◽

Cara M. Rogers ◽

Sandeep Mittal

Keyword(s):

Newcastle Disease Virus ◽

Disease Virus ◽

Newcastle Disease ◽

Tumor Vaccine ◽

Oncolytic Viruses ◽

In Vivo Studies ◽

Term Survival ◽

Dismal Prognosis

Glioblastoma is the most frequent primary brain tumor in adults, with a dismal prognosis despite aggressive resection, chemotherapeutics, and radiotherapy. Although understanding of the molecular pathogenesis of glioblastoma has progressed in recent years, therapeutic options have failed to significantly change overall survival or progression-free survival. Thus, researchers have begun to explore immunomodulation as a potential strategy to improve clinical outcomes. The application of oncolytic virotherapy as a novel biological to target pathogenic signaling in glioblastoma has brought new hope to the field of neuro-oncology. This class of immunotherapeutics combines selective cancer cell lysis prompted by virus induction while promoting a strong inflammatory antitumor response, thereby acting as an effective in situ tumor vaccine. Several investigators have reported the efficacy of experimental oncolytic viruses as demonstrated by improved long-term survival in cancer patients with advanced disease. Newcastle disease virus (NDV) is one of the most well-researched oncolytic viruses known to affect a multitude of human cancers, including glioblastoma. Preclinical in vitro and in vivo studies as well as human clinical trials have demonstrated that NDV exhibits oncolytic activity against glioblastoma, providing a promising avenue of potential treatment. Herein, the authors provide a detailed discussion on NDV as a mode of therapy for glioblastoma. They discuss the potential therapeutic pathways associated with NDV as demonstrated by in vitro and in vivo experiments as well as results from human trials. Moreover, they discuss current challenges, potential solutions, and future perspectives in utilizing NDV in the treatment of glioblastoma.

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