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Viruses May 2024Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome that belongs to the Paramyxoviridae family. While primarily pathogenic... (Review)
Review
Newcastle disease virus (NDV) is an avian pathogen with an unsegmented negative-strand RNA genome that belongs to the Paramyxoviridae family. While primarily pathogenic in birds, NDV presents no threat to human health, rendering it a safe candidate for various biomedical applications. Extensive research has highlighted the potential of NDV as a vector for vaccine development and gene therapy, owing to its transcriptional modularity, low recombination rate, and lack of a DNA phase during replication. Furthermore, NDV exhibits oncolytic capabilities, efficiently eliciting antitumor immune responses, thereby positioning it as a promising therapeutic agent for cancer treatment. This article comprehensively reviews the biological characteristics of NDV, elucidates the molecular mechanisms underlying its oncolytic properties, and discusses its applications in the fields of vaccine vector development and tumor therapy.
Topics: Newcastle disease virus; Animals; Humans; Genetic Vectors; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Genetic Therapy; Viral Vaccines; Newcastle Disease; Vaccine Development
PubMed: 38932177
DOI: 10.3390/v16060886 -
Avian Pathology : Journal of the W.V.P.A Jun 2024The within the family includes at least 22 different species, and is known to cause different types of infections and even be fatal in multiple avian species. There is...
The within the family includes at least 22 different species, and is known to cause different types of infections and even be fatal in multiple avian species. There is limited knowledge of the genetic and biological information of species -2 to 22 in domestic and wild birds and the disease significance of these viruses in birds is not fully determined, although as many as 10 new distinct species have been identified from wild birds and domestic poultry around the world in the last decade. This study aimed to use PCR, virus isolation, and sequencing to genetically and biologically characterize (AOAV-16) in wild birds and domestic poultry collected from different locations in China between 2014 and 2022. Of five isolated AOAV-16 strains (Y1 to Y5), only the Y4 strain had a hemagglutination (HA)-negative result. All of these isolates were low virulent viruses for chickens, except Y3 which was detected simultaneously with avian influenza virus (AIV) of H9N2 subtype. Furthermore, at least four different types of intergenic sequences (IGS) between the HN and L genes junction, and the recombination event as well as interspecific transmission by wild migratory birds, existed within the species AOAV-16. These findings and results of other reported AOAV-16 strains recommend strict control measures to limit contact between wild migratory birds and domestic poultry and imply potential threats to commercial poultry and even public health challenges worldwide.
PubMed: 38922304
DOI: 10.1080/03079457.2024.2373366 -
Frontiers in Immunology 2024Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current...
Newcastle disease virus vector-based SARS-CoV-2 vaccine candidate AVX/COVID-12 activates T cells and is recognized by antibodies from COVID-19 patients and vaccinated individuals.
INTRODUCTION
Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system.
METHODS
This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations.
RESULTS
Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells.
DISCUSSION
The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.
Topics: Humans; COVID-19; SARS-CoV-2; Antibodies, Viral; Newcastle disease virus; COVID-19 Vaccines; Spike Glycoprotein, Coronavirus; Lymphocyte Activation; Adult; Female; Male; Middle Aged; T-Lymphocytes; BNT162 Vaccine; Vaccination; Genetic Vectors; Interferon-gamma
PubMed: 38873610
DOI: 10.3389/fimmu.2024.1394114 -
Applied Microbiology and Biotechnology Jun 2024Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to...
Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log (approximately 1.1 log). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.
Topics: Newcastle disease virus; Pilot Projects; Newcastle Disease; Viral Vaccines; Vacuum; Animals; Temperature; Chickens; Desiccation; China; Drug Stability; Viral Load
PubMed: 38836885
DOI: 10.1007/s00253-024-13174-7 -
Archives of Razi Institute Dec 2023Newcastle disease (ND) is an economically significant and extremely spreadable viral illness affecting a wide variety of avian species. ND can rapidly spread within...
Newcastle disease (ND) is an economically significant and extremely spreadable viral illness affecting a wide variety of avian species. ND can rapidly spread within poultry farms and result in considerable economic losses for the global poultry industry. This disease is endemic in Iran, and despite intensive vaccination efforts in the poultry industry, outbreaks of ND occur unexpectedly. This study aimed to isolate the Newcastle disease virus (NDV) from poultry farms with breathing problems in Markazi province, Iran, and investigate the evolutionary relationship and molecular characteristics of the isolates during 2017-2019. To this end, tissue samples (lung, brain, and trachea) were taken from 42 broiler farms exhibiting respiratory symptoms. The samples were inoculated into 9-11-day-old embryonated eggs, and the virus was isolated from 20 (47.6%) of the 42 farms. Subsequently, RT-PCR was used to amplify partial fusion gene sequences from the new isolates. The amplified products were sequenced and compared phylogenetically to the standard pilot dataset (125 selected sequences) generated by the NDV consortium. As determined by phylogenetic analysis, all nine isolates belonged to subgenotype VII.1.1 of genotype VII and were highly similar to isolates from other parts of Iran and China. Moreover, all isolates possessed a polybasic cleavage site motif (112RRQKRF117), characteristic of virulent strains. Furthermore, the present isolates shared a high nucleotide identity (96%) with viruses previously isolated from other provinces of Iran, as determined by BLAST searches and multiple alignments. In addition, they shared a high degree of sequence similarity but were distinct from the existing NDV vaccines. Therefore, the genetic dissimilarity between current vaccine strains and circulating NDVs must be considered in vaccination programs.
Topics: Animals; Iran; Newcastle disease virus; Newcastle Disease; Chickens; Poultry Diseases; Phylogeny; Viral Fusion Proteins; Genotype
PubMed: 38828167
DOI: 10.32592/ARI.2023.78.6.1794 -
Archives of Razi Institute Dec 2023The Newcastle disease virus (NDV) is a member of the paramyxoviridea family and has great significance in the poultry production industry, which spends a huge amount of...
The Newcastle disease virus (NDV) is a member of the paramyxoviridea family and has great significance in the poultry production industry, which spends a huge amount of money every year on prevention and economic loss caused by this disease. A wide range of symptoms, including respiratory and nervous disorders, as well as hemorrhage lesions in the digestive system are observed in this disease. This research investigated the presence of NDV in 10 poultry farms with high mortality and respiratory symptoms in Kerman province, Iran (between January 2020 to October 2020). Tissue samples were collected from mortalities of 10 flocks in different parts of Kerman province and inoculated into embryonated eggs. The NDV was detected in the allantoic fluid by polymerization of partial F gene protein. The virus was positive in the samples of 5 flocks. The results of the phylogenetic analysis also showed that the sequence of isolates was related to genotype II (three isolates) and sub-genotype VIId (two isolates) of NDVs. It was also found that the amino acid sequences of sub-genotype VIId isolates in the 113 to 116 positions were RRQKR and in the 117 positions was the presence of F (phenylalanine). The other three isolates were grouped with B1, Clone, and LaSota vaccines, and the amino acid sequence in the cleavage site included GRQGRL. The similarity between the studied isolates was 99.6%-98.4%. In this study, virulent viruses were isolated and tracked in broiler farms that were vaccinated with live and killed vaccines. It is recommended to pay more attention to designing the vaccination program.
Topics: Animals; Newcastle disease virus; Chickens; Newcastle Disease; Poultry Diseases; Iran; Phylogeny; Genotype
PubMed: 38828165
DOI: 10.32592/ARI.2023.78.6.1860 -
International Immunopharmacology Jul 2024The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional...
The second-leading cause of death, cancer, poses a significant threat to human life. Innovations in cancer therapies are crucial due to limitations in traditional approaches. Newcastle disease virus (NDV), a nonpathogenic oncolytic virus, exhibits multifunctional anticancer properties by selectively infecting, replicating, and eliminating tumor cells. To enhance NDV's antitumor activity, four oncolytic NDV viruses were developed, incorporating IL24 and/or GM-CSF genes at different gene loci using reverse genetics. In vitro experiments revealed that oncolytic NDV virus augmented the antitumor efficacy of the parental virus rClone30, inhibiting tumor cell proliferation, inducing tumor cell fusion, and promoting apoptosis. Moreover, NDV carrying the IL24 gene inhibited microvessel formation in CAM experiments. Evaluation in a mouse model of liver cancer confirmed the therapeutic efficacy of oncolytic NDV viral therapy. Tumors in mice treated with oncolytic NDV virus significantly decreased in size, accompanied by tumor cell detachment and apoptosis evident in pathological sections. Furthermore, oncolytic NDV virus enhanced T cell and dendritic cell production and substantially improved the survival rate of mice with hepatocellular carcinoma, with rClone30-IL24(P/M) demonstrating significant therapeutic effects. This study establishes a basis for utilizing oncolytic NDV virus as an antitumor agent in clinical practice.
Topics: Animals; Newcastle disease virus; Oncolytic Virotherapy; Oncolytic Viruses; Humans; Mice; Cell Line, Tumor; Interleukins; Liver Neoplasms; Mice, Inbred BALB C; Carcinoma, Hepatocellular; Apoptosis; Neovascularization, Pathologic; Cell Proliferation; Granulocyte-Macrophage Colony-Stimulating Factor; Dendritic Cells; T-Lymphocytes
PubMed: 38823178
DOI: 10.1016/j.intimp.2024.112305 -
Methods in Molecular Biology (Clifton,... 2024Vectored RNA vaccines offer a variety of possibilities to engineer targeted vaccines. They are cost-effective and safe, but replication competent, activating the humoral... (Review)
Review
Vectored RNA vaccines offer a variety of possibilities to engineer targeted vaccines. They are cost-effective and safe, but replication competent, activating the humoral as well as the cellular immune system.This chapter focuses on RNA vaccines derived from negative-strand RNA viruses from the order Mononegavirales with special attention to Newcastle disease virus-based vaccines and their generation. It shall provide an overview on the advantages and disadvantages of certain vector platforms as well as their scopes of application, including an additional section on experimental COVID-19 vaccines.
Topics: Animals; Humans; COVID-19; Genetic Vectors; Newcastle disease virus; RNA Viruses; SARS-CoV-2; Viral Vaccines; mRNA Vaccines
PubMed: 38814390
DOI: 10.1007/978-1-0716-3770-8_3 -
Microbial Pathogenesis Jul 2024Newcastle disease virus (NDV) is the pathogen of a zoonosis that is primarily transmitted by poultry and has severe infectivity and a high fatality rate. Many studies...
Newcastle disease virus (NDV) is the pathogen of a zoonosis that is primarily transmitted by poultry and has severe infectivity and a high fatality rate. Many studies have focused on the role of the NDV fusion (F) protein in the cell-cell membrane fusion process. However, little attention has been given to the heptad repeat region, HR4, which is located in the NDV F2 subunit. Here, site-directed mutants were constructed to study the function of the NDV F protein HR4 region and identify the key amino acids in this region. Nine conserved amino acids were substituted with alanine or the corresponding amino acid of other aligned paramyxoviruses. The desired mutants were examined for changes in fusogenic activity through three kinds of membrane fusion assays and expression and proteolysis through IFA, FACS and WB. The results showed that when conserved amino acids (L81, Y84, L88, L91, L92, P94, L95 and I99) were replaced with alanine, the fusogenic activity of the F protein was abolished, possibly because of failed protein expression not only on the cell surface but also inside cells. These data indicated that the conserved amino acids above in NDV F HR4 are critical for normal protein synthesis and expression, possibly for the stability of the F protein monomer, formation of trimer and conformational changes.
Topics: Newcastle disease virus; Viral Fusion Proteins; Animals; Virus Internalization; Mutagenesis, Site-Directed; Amino Acid Substitution; Cell Line; Mutation; Proteolysis; Membrane Fusion
PubMed: 38810765
DOI: 10.1016/j.micpath.2024.106713 -
Viruses May 2024The emergence of new virulent genotypes and the continued genetic drift of Newcastle disease virus (NDV) implies that distinct genotypes of NDV are simultaneously... (Review)
Review
The emergence of new virulent genotypes and the continued genetic drift of Newcastle disease virus (NDV) implies that distinct genotypes of NDV are simultaneously evolving in different geographic locations across the globe, including throughout Africa, where NDV is an important veterinary pathogen. Expanding the genomic diversity of NDV increases the possibility of diagnostic and vaccine failures. In this review, we systematically analyzed the genetic diversity of NDV genotypes in Africa using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Information published between 1999 and 2022 were used to obtain the genetic background of different genotypes of NDV and their geographic distributions in Africa. The following genotypes were reported in Africa: I, II, III, IV, V, VI, VII, VIII, XI, XIII, XIV, XVII, XVIII, XX, and XXI. A new putative genotype has been detected in the Democratic Republic of the Congo. However, of 54 African countries, only 26 countries regularly report information on NDV outbreaks, suggesting that this number may be vastly underestimated. With eight different genotypes, Nigeria is the country with the greatest genotypic diversity of NDV among African countries. Genotype VII is the most prevalent group of NDV in Africa, which was reported in 15 countries. A phylogeographic analysis of NDV sequences revealed transboundary transmission of the virus in Eastern Africa, Western and Central Africa, and in Southern Africa. A regional and continental collaboration is recommended for improved NDV risk management in Africa.
Topics: Newcastle disease virus; Genotype; Genetic Variation; Newcastle Disease; Africa; Animals; Phylogeny; Genome, Viral; Vaccination; Chickens; Viral Vaccines; Poultry Diseases; Phylogeography
PubMed: 38793675
DOI: 10.3390/v16050795