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1.
Gene ; 766: 145077, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32941951

RESUMO

Newcastle disease virus (NDV) is a contagious poultry paramyxovirus, leading to substantial economic losses to the poultry industry. Here, RNA-seq was carried out to investigate the altered expression of immune-related genes in chicken thymus within 96 h in response to NDV infection. In NDV-infected chicken thymus tissues, comparative transcriptome analysis revealed 1386 differentially expressed genes (DEGs) at 24 h with 989 up- and 397 down-regulated genes, 728 DEGs at 48 h with 567 up- and 161 down-regulated genes, 1514 DEGs at 72 h with 1016 up- and 498 down-regulated genes, and 1196 DEGs at 96 h with 522 up- and 674 down-regulated genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these candidate targets mainly participate in biological processes or biochemical, metabolic and signal transduction processes. Notably, there is large enrichment in biological processes, cell components and metabolic processes, which may be related to NDV pathogenicity. In addition, the expression of five immune-related DEGs identified by RNA-seq was validated by quantitative real-time polymerase chain reaction (qRT-PCR). Our results indicated that the expression levels of AvBD5, IL16, IL22 and IL18R1 were obviously up-regulated, and Il-18 expression was also changed, but not significantly, which play key roles in the defense against NDV. Overall, we identified several candidate targets that may be involved in the regulation of NDV infection, which provide new insights into the complicated regulatory mechanisms of virus-host interactions, and explore new strategies for protecting chickens against the virus.


Assuntos
Galinhas/genética , Galinhas/imunologia , Doença de Newcastle/genética , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Transcriptoma/genética , Vacinas Virais/imunologia , Animais , Galinhas/virologia , Regulação para Baixo/imunologia , Perfilação da Expressão Gênica/métodos , Doença de Newcastle/virologia , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Análise de Sequência de RNA/métodos , Transcriptoma/imunologia , Regulação para Cima/imunologia
2.
Poult Sci ; 99(9): 4351-4359, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32867979

RESUMO

The vaccines currently available to control infectious bursal disease (IBD) include live-attenuated and inactivated vaccines, immune-complex vaccines, and vaccines consisting of viral constructs of herpesvirus of turkeys genetically engineered to express VP2 surface protein. To evaluate the impact of vaccines on the chicken immune system, 2 animal trials were performed in specific pathogen-free broiler chickens. In trial 1, birds were either vaccinated when they are one-day old with a dual recombinant herpes virus of turkey construct vaccine, expressing VP2 protein of (IBDV) and F protein of Newcastle disease virus, or an immune-complex IBDV vaccine or birds were not vaccinated. At 14, 28, and 35 D, the bursa of Fabricius was collected for bursa:body weight (B:BW) ratio calculation. In trial 2, birds were vaccinated when they were 1-day old according to the same protocol as trial 1, but at day 14, all groups also received a live infectious bronchitis (IB) vaccine. At 0, 7, 14, 21, and 28 days after IB vaccination, birds were tested by ELISA for IB serology and, soon after the last blood sampling, they were euthanized for collection of Harderian glands, trachea, and spleen and testing by flow cytometry for characterization of mononuclear cells. The immune-complex vaccine groups showed significantly lower B:BW ratio, lower IBV antibody titers, and higher mean percentage of CD8+ T cells in the spleen, trachea, and Harderian glands than those in the other experimental groups. The results of the in vivo trials coupled with a depth analysis of the repertoire of parameters involved in the immune response to IBD and IB vaccinations show one vaccine may influence the immune response of other vaccines included in the vaccination program.


Assuntos
Infecções por Birnaviridae/veterinária , Doenças das Aves Domésticas/imunologia , Vacinas Virais/imunologia , Animais , Infecções por Birnaviridae/imunologia , Bolsa de Fabricius/patologia , Galinhas , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/veterinária , Vírus da Bronquite Infecciosa/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Vacinação/veterinária , Vacinas Atenuadas/imunologia
3.
Arch Virol ; 165(9): 1959-1968, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32519007

RESUMO

Newcastle disease (ND), caused by virulent Newcastle disease virus (NDV) strains, has been one of the most problematic diseases affecting the poultry industry worldwide. Conventional vaccines provide effective protection for birds to survive ND outbreaks, but they may not completely suppress NDV shedding. NDV strains circulate on farms for a long time after the initial infection and cause potential risks. A new vaccine with fast clearance ability and low viral shedding is needed. In this study, we used interleukin-12 (IL-12) as an adjuvant and electroporation (EP) as an advanced delivery system to improve a DNA vaccine candidate. The fusion (F) protein gene from an NDV strain of the prevalent genotype VII.1.1 was cloned to prepare the vaccine. Chickens immunized with the F gene DNA vaccine co-delivered with an IL-12-expressing plasmid DNA showed higher neutralizing antibody levels and stronger concanavalin-A-induced lymphocyte proliferation than those treated with the F gene DNA vaccine alone. The co-delivered vaccine provided 100% protection, and less viral shedding and a shorter release time were observed in challenged chickens than when the F gene DNA vaccine was administered alone. The use of F gene DNA combined with IL-12 delivered by electroporation is a promising approach for vaccination against ND.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Interleucina-12/imunologia , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinas de DNA/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Galinhas , Eletroporação , Interleucina-12/administração & dosagem , Doença de Newcastle/imunologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/genética , Vírus da Doença de Newcastle/fisiologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Vacinação , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética , Proteínas Virais de Fusão/administração & dosagem , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Eliminação de Partículas Virais
4.
Sci Rep ; 10(1): 6155, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32273535

RESUMO

Newcastle disease virus (NDV) replication depends on the translation machinery of the host cell; therefore, the eukaryotic translation initiation factor 2 (eIF2) gene family is a likely candidate for control of viral replication. We hypothesized that differential expression of host genes related to translation and innate immune response could contribute to differential resistance to NDV in inbred Fayoumi and Leghorn lines. The expression of twenty-one genes related to the interferon signaling pathway and the eIF2 family was evaluated at two- and six-days post infection (dpi) in the spleen from both lines, either challenged by NDV or nonchallenged. Higher expression of OASL in NDV challenged versus nonchallenged spleen was observed in Leghorns at 2 dpi. Lower expression of EIF2B5 was found in NDV challenged than nonchallenged Fayoumis and Leghorns at 2 dpi. At 2 dpi, NDV challenged Fayoumis had lower expression of EIF2B5 and EIF2S3 than NDV challenged Leghorns. At 6 dpi, NDV challenged Fayoumis had lower expression of EIF2S3 and EIF2B4 than NDV challenged Leghorns. The genetic line differences in expression of eIF2-related genes may contribute to their differential resistance to NDV and also to understanding the interaction between protein synthesis shut-off and virus control in chickens.


Assuntos
Galinhas/genética , Fator de Iniciação 2 em Eucariotos/genética , Imunidade Inata/genética , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Animais , Cruzamento , Galinhas/imunologia , Galinhas/virologia , Resistência à Doença/genética , Resistência à Doença/imunologia , Fator de Iniciação 2 em Eucariotos/fisiologia , Imunidade Inata/imunologia , Baço/imunologia , Baço/fisiopatologia
5.
Poult Sci ; 99(4): 1896-1905, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241469

RESUMO

This study was conducted to assess the growth performance and immunological effects of vaccination-induced stress on broilers. The chickens were administered 0, 2, 4, 8, and 16 doses of live LaSota Newcastle disease (ND) vaccine and slaughtered on the 1st, 7th, 14th, and 21st day post vaccination. The results showed that the serum antibody titers after Newcastle disease virus (NDV) vaccination were elevated at day 7 post vaccination, peaked at day 14, then declined by day 21. Interestingly, the antibody titers peaked at 2 doses, and no further dose-dependent titer increases were observed. This study demonstrated that vaccination-induced stress increased serum adrenocorticotropic hormone and cortisol, affected growth performance (average daily gain, average daily feed intake, and feed conversion ratio), and triggered apoptosis in spleen lymphocytes by downregulating the ratio of Bcl-2 to BAX and upregulating the gene expressions of caspase-3 and -9, which was concordant with the activation of the enzymatic activities of caspase-3 and -9. This study suggests that NDV vaccine doses in broilers must be controlled judiciously because increasing the number of doses resulted in increased lymphocyte apoptosis while the peak of the antibody titer and optimal growth performance were achieved at a low number of doses (2 doses).


Assuntos
Galinhas/imunologia , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Vacinação/veterinária , Vacinas Virais/efeitos adversos , Animais , Galinhas/crescimento & desenvolvimento , Feminino , Masculino , Estresse Fisiológico
6.
Poult Sci ; 99(4): 1921-1927, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241472

RESUMO

The present study aimed to evaluate the immunopotentiating effect of plant-derived soyasaponin and its immunogenicity in chickens challenged with Newcastle disease virus (NDV). Soyasaponin was extracted from soybean seeds and detected using the phytochemical tests, followed by quantification through the dry-weight method. One-day-old broiler chicks (n = 90) were divided into 3 groups, named as A, B, and C. Group A birds were orally administrated with soyasaponin (5 mg/kg), followed by immunization with inactivated ND vaccine intramuscularly (IM), whereas group B birds were vaccinated with inactivated ND vaccine alone. Group C birds were kept unvaccinated. A booster dose on day 21 was also administered IM to group A and B birds. At day 35, all 3 groups were challenged with NDV. To determine the immunogenicity potential of soyasaponin, antibody titer was measured using the hemagglutination inhibition test before and after the NDV challenge. Histochemical examination was performed to determine the pathological changes associated with NDV infection. Foam formation and hemolytic activity confirmed the presence of saponin in soya bean extract. Group A birds showed a higher antibody response compared with group B and C birds. The disease challenge study showed that soyasaponin-adjuvanted NDV vaccine provided complete protection to group A birds against ND. Moreover, no side effects of soyasaponin were observed on the growth performance of birds during the experiment. Therefore, we can conclude that soyasaponin is a potential immunogenic agent and therefore could be a promising candidate to launch a protective humoral response against ND in chickens.


Assuntos
Galinhas , Imunidade Humoral/efeitos dos fármacos , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Substâncias Protetoras/farmacologia , Saponinas/farmacologia , Vacinas Virais/administração & dosagem , Administração Oral , Animais , Substâncias Protetoras/administração & dosagem , Saponinas/administração & dosagem , Soja/química , Vacinas de Produtos Inativados/administração & dosagem
7.
Avian Dis ; 64(1): 53-59, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32267125

RESUMO

Recombinant Newcastle disease virus (NDV) LaSota (LS) expressing secreted trimeric spike (S)-ectodomain (Se) of infectious bronchitis virus (IBV) (rLS/IBV.Se) was developed and evaluated for protection conferred against IBV challenge. The IBV S-ectodomain protein, which is S excluding the transmembrane anchor and short cytoplasmic domain of S2, expressed from recombinant LS corresponds to an Arkansas (Ark)-type IBV. In a first experiment, chickens were primed at 1 day of age or primed at 1 day of age and boosted at 14 days of age with 104 50% embryo infectious doses (EID50)/bird of rLS/IBV.Se and challenged with a virulent Ark strain. A single vaccination proved completely ineffective at protecting chickens against challenge, whereas priming and boosting reduced clinical signs and tracheal lesions but did not reduce viral load in lachrymal fluids. In experiment 2, the vaccine dose was increased to 107 EID50/bird and a different virulent Ark strain was used for challenge. In addition, chickens were singly immunized on either day 1 or day 10 after hatch. NDV antibody levels detected in vaccinated chickens were moderate, with hemagglutination inhibition titers varying between 4 and 5 log2. Slightly higher antibody levels to NDV were observed in chickens vaccinated on day 10 versus day 1 but without the difference achieving statistical significance. In contrast, antibody responses measured using recombinant IBV S1 protein-coated ELISA plates were significantly greater in chickens vaccinated on day 10 than on day 1. The use of a higher rLS/IBV.Se dose substantially enhanced the success of a single vaccination compared to experiment 1. Signs and tracheal lesions were reduced more effectively in chickens vaccinated at day 10 after hatch. However, as in experiment 1, vaccination did not reduce the viral loads in tear fluids of challenged chickens. Similar results, in which no reduction in viral load in the trachea was apparent from rLS/IBV.S vaccination, have been obtained by others. Further work is needed to understand the immune responses induced by this recombinant virus that seems to provide some protection against the disease but does not reduce viral loads in the upper respiratory tract.


Assuntos
Galinhas , Infecções por Coronavirus/veterinária , Vírus da Bronquite Infecciosa/imunologia , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Virais/imunologia , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Vacinas Sintéticas/imunologia
8.
Arch Razi Inst ; 75(1): 1-7, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32291996

RESUMO

Newcastle disease causes many economic losses to the poultry industry in most countries. This disease is endemic in Iran. Backyard poultry is considered the reservoir of Newcastle virus; however, there is either no vaccination program against Newcastle, or it is performed in a restricted manner. Commercial live vaccines are inactive and sensitive to temperature; moreover, vaccine delivery to villages and remote areas requires special equipment and high cost to maintain the cold chain. This study evaluated the effectiveness of a thermostable Newcastle vaccine produced by the Razi Institute (ND.TR.IR) on the backyard poultry. In four provinces, at least 4 villages were selected as the treatment group, and the same number was selected as the control group. At least, 30 birds were sampled in each village. In each group, blood samples were collected before vaccination and 2 weeks later, and the serum titer of the samples was examined with the haemagglutination inhibition test. The arithmetic mean and standard deviation of the sample titers at the rural level were compared using paired t-test before and after vaccination in each group. Moreover, Repeated Measures ANOVA was utilized to compare the vaccinated and control groups in terms of the titer changes before and after vaccination. In this study, 584 and 389 samples were taken from the treatment (53 households in 20 villages) and control groups (33 households in 14 villages). The mean serum titer values of Newcastle were 4.51±3.03 and 6.64±2.48 in the treatment group before and after vaccination, respectively (P<0.001). The increase in mean titer of the treatment group (2.31 log) was statistically higher than that in the control group (0.66 log) (P<0.001). Out of 584 birds, 517 (88.5%) ones had titer above 3 in the second turn in the treatment group. The thermostable vaccine (ND.TR.IR) produced by the Razi institute is suitable for backyard poultry, which immunizes them against Newcastle disease. Appropriate vaccination programs for backyard poultry should be made; moreover, vaccination of backyard poultry can be effective in preventing the circulation of the field viruses.


Assuntos
Galinhas , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Vacinas Virais/imunologia , Animais , Irã (Geográfico) , Doença de Newcastle/virologia , Doenças das Aves Domésticas/virologia , Vacinas Virais/administração & dosagem , Vacinas Virais/química
9.
Arch Razi Inst ; 75(1): 31-37, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32292000

RESUMO

Newcastle disease (ND) is a major threat to poultry industry production throughout developing countries. The Newcastle disease viruses (NDVs) infecting industrialized and indigenous poultry in Iran are velogenic strains and responsible for the frequent outbreaks of ND in poultry farms even in vaccinated flocks causing serious economic losses in the commercial and indigenous poultry. However, vaccination is the only way to protect against endemic ND, and the conventional vaccines are not heat stable and consequently require complex cold-chains to be transferred to users leading to not much resistance. The present study aimed to evaluate the efficacy of thermostable NDV strain I-2 in broiler chickens vaccinated via drinking water and coated on oiled wheat grain. The horizontal transmission of I-2 strain and transmission of disease from vaccinated to unvaccinated chickens were also evaluated in this study. The obtained results showed that both routes of administration, following primary and/or secondary dose, provoked the production of necessary antibody titer and adequate protective immunity in broiler chickens. Moreover, the horizontal transmission of I-2 strain from vaccinated to unvaccinated chickens housed together induced an antibody response and protected unvaccinated chickens against a local field isolate of a virulent strain of NDV (The intravenous pathogenicity index 2.46, mean death time 59 h). Nevertheless, all unvaccinated and Newcastle challenged broilers chickens against the NDV died in this study. It is noteworthy that the transmission of the virus from challenged broiler chickens was very low to induce clinical signs in susceptible chickens. The obtained results of this study revealed the efficacy of NDV strain I-2 coated on the oiled wheat and via drinking water as it protects broiler chickens from highly virulent NDV.


Assuntos
Galinhas , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Vacinas Virais/farmacologia , Animais , Anticorpos Antivirais/sangue , Formação de Anticorpos , Irã (Geográfico) , Doença de Newcastle/imunologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/patogenicidade , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/virologia , Vacinas Virais/administração & dosagem , Vacinas Virais/química
10.
Mol Biotechnol ; 62(6-7): 344-354, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32246385

RESUMO

Newcastle disease (ND) is considered as one of the most devastating infectious diseases targeting domestic birds and has considerable threat to the commercial poultry production. Two surface glycoproteins, hemagglutinin-neuraminidase (HN) and fusion (F), act as antigens in the virus structure and also play important roles in infecting host cells. In the current study, the expression of the chimeric HN-F protein in canola seeds and its immunogenicity in chickens were investigated. The HN-F gene was cloned downstream of the fatty acid elongase 1 (FAE1) promoter in the binary expression vector, pBI1400-HN-F, and introduced into rapeseed (Brassica napus L.) using Agrobacterium-mediated transformation. The amount of the HN-F glycoprotein was estimated up to 0.18% and 0.11% of the total soluble protein (TSP) in transgenic seeds and leaves of canola, respectively. Confirmatory analyses of 36 transgenic lines revealed that the HN-F gene was integrated into the genome. Subsequently, HN-F protein could be expressed and accumulated in the seed tissue. Specific pathogen-free (SPF) chickens immunized orally with recombinant HN-F showed a significant rise in specific and hemagglutination inhibition (HI) antibodies 35 to 42 days post the first administration. The results implied the potential of transgenic canola seed-based expression for oral delivery of NDV immunogenic glycoproteins.


Assuntos
Brassica napus/química , Proteína HN/imunologia , Vírus da Doença de Newcastle/imunologia , Óleos Vegetais/química , Plantas Geneticamente Modificadas/química , Sementes/química , Animais , Galinhas , Elongases de Ácidos Graxos/genética , Elongases de Ácidos Graxos/metabolismo , Folhas de Planta/química
11.
Poult Sci ; 99(3): 1275-1286, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32111305

RESUMO

Newcastle disease virus (NDV) is a major threat to the poultry industry worldwide, with a diversity of genotypes associated with severe economic losses in all poultry sectors. Class II genotype VII NDV are predominant in the Middle East and Asia, despite intensive vaccination programs using conventional live and inactivated NDV vaccines. In Egypt, the disease is continuously spreading, causing severe economical losses in the poultry industry. In this study; the protective efficacy of a commercial, inactivated recombinant genotype VII NDV-matched vaccine (KBNP-C4152R2L strain) against challenge with the velogenic NDV strain (Chicken/USC/Egypt/2015) was evaluated in commercial layers. Two vaccination regimes were used; live NDV genotype II (LaSota) vaccine on days 10, 18, and 120, with either the inactivated NDV genotype II regime or inactivated NDV genotype VII-matched vaccine regime on days 14, 42, and 120. The 2 regimes were challenged at the peak of egg production on week 26. Protection by the 2 regimes was evaluated after experimental infection, based on mortality rate, clinical signs, gross lesions, virus shedding, seroconversion, and egg production schedule. The results show that these 2 vaccination regimes protected commercial layer chickens against mortality, but some birds showed mild clinical signs and reduced egg production temporarily. However, the combination of live NDV genotype II and recombinant inactivated genotype VII vaccines provided better protection against virus shedding (20% and 0% vs. 60% and 40%) as assessed in tracheal swabs and (20% and 0% vs. 20% and 20%) in cloacal swabs collected at 3 and 5 D post challenge (dpc), respectively. In addition, egg production levels in birds receiving the inactivated NDV genotype VII-matched vaccine regime and in those given inactivated genotype II vaccines were 76.6, 79, 82, and 87.4% and 77.7, 72.5, 69, and 82.5% at 7, 14, 21, and 28 dpc, respectively. The results of this study indicate that recombinant genotype-matched inactivated vaccine along with a live attenuated vaccine can reduce virus shedding and improve egg production in commercial layers challenged with a velogenic genotype VII virus under field conditions. This regime may ensure a proper control strategy in layers.


Assuntos
Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinação/tendências , Vacinação/veterinária , Vacinas Virais/administração & dosagem , Animais , Galinhas , Egito , Feminino , Genótipo , Vírus da Doença de Newcastle/genética , Vacinas Atenuadas/administração & dosagem , Vacinas Sintéticas/administração & dosagem
12.
J Gen Virol ; 101(5): 473-483, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32209169

RESUMO

Newcastle disease virus (NDV) vectors expressing avian influenza virus (AIV) haemagglutinin (HA) of subtype H5 simultaneously protect chickens from Newcastle disease (ND) as well as avian influenza (AI). The expressed, membrane-bound surface protein HA is incorporated into virions while soluble HA has been described as a potent antigen. We tested whether co-expression of both HA variants from the same NDV vector increased the overall level of HA, which could be important for optimal immunogenicity. Recombinant NDVsolH5_H5 co-expressed membrane-bound H5 of highly pathogenic (HP) AIV H5N1, detectable in infected cells, and soluble H5, which was secreted into the supernatant. This virus was compared to recombinant NDV that express either membrane-bound (rNDVH5) or soluble H5 (rNDVsolH5). Replication in embryonated chicken eggs (ECEs) and in cell culture, as well as pathogenicity in ECEs, was not influenced by the second heterologous transcriptional unit. However, the co-expression of soluble H5 with membrane-bound H5 increased total protein level about 5.25-fold as detected by MS quantification. Hence, this virus is very interesting as a vaccine virus in chickens against HPAIV infections in situations in which previous H5-expressing NDVs have reached their limit, such as in the face of pre-existing AIV maternal immunity.


Assuntos
Antígenos Virais/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Influenza Aviária/imunologia , Vírus da Doença de Newcastle/imunologia , Animais , Anticorpos Antivirais/imunologia , Linhagem Celular , Galinhas , Cricetinae , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/imunologia , Doença de Newcastle/imunologia , Eliminação de Partículas Virais/imunologia
13.
Cell Immunol ; 349: 104043, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32044112

RESUMO

Type I Interferon (IFN) signaling plays a critical role in dendritic cell (DC) development and functions. Inhibition of hyper type I IFN signaling promotes cDC2 subtype development. Relb is essential to development of cDC2 subtype and here we analyzed its effect on type I IFN signaling in DCs. We show that Relb suppresses the homeostatic type I IFN signaling in cDC2 cultures. TLR stimulation of FL-DCs led to RelB induction coinciding with fall in IFN signatures; conforming with the observation Relb expression reduced TLR stimulated IFN induction along with decrease in ISGs. Towards understanding mechanism, we show that effects of RelB are mediated by increased levels of IκBα. We demonstrate that RelB dampened antiviral responses by lowering ISG levels and the defect in cDC2 development in RelB null mice can be rescued in Ifnar1-/- background. Overall, we propose a novel role of RelB as a negative regulator of the type I IFN signaling pathway; fine tuning development of cDC2 subtype.


Assuntos
Células Dendríticas/imunologia , Interferon Tipo I/imunologia , Inibidor de NF-kappaB alfa/fisiologia , Fator de Transcrição RelB/fisiologia , Sequência de Aminoácidos , Animais , Diferenciação Celular , Células Cultivadas , Cruzamentos Genéticos , Células Dendríticas/classificação , Células Dendríticas/citologia , Regulação da Expressão Gênica/imunologia , Camundongos , Células NIH 3T3 , Vírus da Doença de Newcastle/imunologia , Peptídeos/farmacologia , Receptor de Interferon alfa e beta/deficiência , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/fisiologia , Transdução de Sinais/imunologia , Baço/citologia , Fator de Transcrição RelB/deficiência , Fator de Transcrição RelB/genética , Carga Viral
14.
PLoS One ; 15(2): e0229009, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32045459

RESUMO

Broiler chickens experience an acute-phase response (APR) through vaccination, which reflects the innate immunity and stress related to immunization. It is also considered that APR can modulate adaptive immunity and response to infection. As biomarkers for APR, assessing the acute-phase proteins (APPs) function and their levels in response to immunization is of great value for vaccine design, development and administration. In this study, the heterophils/lymphocyte (H/L) ratio and the level of APPs was evaluated in broilers with three different Newcastle disease (ND) vaccination regimens. Inactivated ND vaccine (IND) was administered by the intramuscular route. Live attenuated strains, Lasota and Vitapest, was administered by ocular routes. H/L ratio, serum amyloid A (SAA) and alpha-1 acid glycoprotein (AGP) were measured before and after two rounds of vaccination on days 10 and 21. In a comparison between the three vaccines, H/L ratio in IND group significantly increased to 3 fold (1.48 ± 0.41) after the first vaccination while the Lasota and Vitapest showed a milder response. The concentration of SAA increased after 24h by 1.8-fold in IND group (0.116 ± 0.015 mg/L) and 2-fold in Lasota group (0.14 ± 0.002 mg/L). Significant changes were found in Vitapest group after 48h post vaccination (0.113 ± 0.016 mg/L). Elevation pattern of AGP, 24 hours after first vaccination in IND (3.5-fold) and Vitapest (2.5-fold) was different from Lasota in which the peak was reached after 48 hours (2.9-fold). Except for IND group, no significant changes in SAA and AGP concentrations were detected after the second vaccination. A significant positive correlation between SAA values at day 22 and HI titers at day 28 (r = 0.998, P≤0. 0.005) was found. According to these results, different types of ND vaccines can cause different patterns of acute phase responses. Assessment of stress and level of acute-phase proteins can be used for prediction of immune response outcomes in vaccine design and development.


Assuntos
Reação de Fase Aguda/imunologia , Proteínas Aviárias/imunologia , Proteínas Sanguíneas/imunologia , Galinhas/imunologia , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Vacinação , Vacinas Virais/imunologia , Animais , Doença de Newcastle/imunologia , Fatores de Tempo
15.
Transbound Emerg Dis ; 67(1): 159-170, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432620

RESUMO

Although Newcastle disease virus (NDV) has a worldwide distribution, some NDV genotypes have more regional geographical ranges within continents. In this study, we isolated a subgenotype XIIb NDV strain, Goose/CH/GD/E115/2017 (E115), from geese in Guangdong province, Southern China, in 2017. Phylogenetic analysis showed that E115 and six other NDVs from geese in China were grouped under subgenotype XIIb and were distinct from subgenotype XIIa, isolated from chickens in South Africa, and subgenotype XIId, isolated from chickens in Vietnam. To better understand the pathogenicity and transmission of the subgenotype XIIb NDVs from geese in Guangdong province, we inoculated chickens and geese with 106 EID50 of the E115 virus. Eight hours after inoculation, three naïve chickens and three naïve geese were co-housed with the infected chickens or geese to assess intraspecific and interspecific horizontal transmission of the E115 virus. The E115 virus induced significant clinical signs without mortality in chickens, while it was not pathogenic to geese. Intraspecific and interspecific horizontal transmission of the E115 virus was observed among chickens and geese via direct contact. Furthermore, although the current vaccines provided complete protection against disease in chickens after challenging them with the E115 virus, the virus could also be transmitted from vaccinated chickens to naïve contact chickens. Collectively, our findings highlight the need for avoiding the mixing of different bird species to reduce cross-species transmission and for surveillance of NDV in waterfowl.


Assuntos
Doenças das Aves/virologia , Galinhas/virologia , Gansos/virologia , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/genética , Vacinação/veterinária , Vacinas Virais/imunologia , Animais , Doenças das Aves/prevenção & controle , Doenças das Aves/transmissão , China/epidemiologia , Feminino , Genótipo , Doença de Newcastle/prevenção & controle , Doença de Newcastle/transmissão , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/patogenicidade , Vírus da Doença de Newcastle/fisiologia , Filogenia , África do Sul/epidemiologia , Organismos Livres de Patógenos Específicos , Vietnã/epidemiologia , Virulência , Eliminação de Partículas Virais
16.
J Virol ; 94(3)2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31694938

RESUMO

Newcastle disease virus (NDV) is an attractive candidate for oncolytic immunotherapy due to its ability to replicate in tumor cells and potentially to overcome the inherently immunosuppressive nature of the tumor microenvironment. The advent of checkpoint blockade immunotherapy over the past few years represents a paradigm shift in cancer therapy. However, the prevalence of severe immune-related adverse events with CTLA4 and PD1 pathway blockade in clinical studies, especially in combination therapy groups, is a cause for concern. Immunotherapies with cytokines have also been extensively explored, but they have been associated with adverse events in clinical trials. Oncolytic vectors engineered to express checkpoint blockade antibodies and cytokines could provide an avenue for reducing the clinical toxicity associated with systemic therapy by concentrating the immunomodulatory payload at the site of disease. In this study, we engineered six different recombinant viruses: NDVs expressing checkpoint inhibitors (rNDV-anti-PD1 and rNDV-anti-PDL1); superagonists (rNDV-anti-CD28); and immunocytokines, where the antibodies are fused to an immunostimulatory cytokine, such as interleukin 12 (IL-12) (rNDV-anti-CD28-murine IL-12 [mIL-12], rNDV-anti-PD1-mIL-12, and rNDV-anti-PDL1-mIL-12). These six engineered viruses induced tumor control and survival benefits in both highly aggressive unilateral and bilateral B16-F10 murine melanoma models, indicative of an abscopal effect. The data represent a strong proof of concept on which further clinical evaluation could build.IMPORTANCE Checkpoint inhibitor therapy has shown tremendous efficacy, but also frequent and often severe side effects-especially when multiple drugs of the class are used simultaneously. Similarly, many investigational immunotherapy agents, which have shown promise in animal models, have failed in clinical trials due to dose-limiting toxicity when administered systemically. This study utilized a murine melanoma model to evaluate the efficacy of intratumoral injections of recombinant NDVs engineered to express multiple immunotherapeutic proteins with well-documented side effects in humans. Our results indicate that intratumoral administration of these recombinant NDVs, particularly when combined with systemic CTLA4 checkpoint inhibition, exerts a robust effect in treated and nontreated tumors, indicative of a systemic antitumoral response. The intratumoral delivery of rNDVs expressing immunotherapeutic proteins may be an effective method of targeting the immune cell populations most relevant for antitumoral immunity and allowing us to restrict the use of systemic immunotherapy agents.


Assuntos
Antineoplásicos/farmacologia , Citocinas/farmacologia , Imunoterapia/métodos , Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/imunologia , Terapia Viral Oncolítica/métodos , Animais , Anticorpos Monoclonais Humanizados/farmacologia , Antígeno CTLA-4 , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Melanoma , Camundongos , Camundongos Endogâmicos C57BL , Doença de Newcastle/virologia , Vírus Oncolíticos , Microambiente Tumoral
17.
Appl Microbiol Biotechnol ; 104(1): 107-117, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734810

RESUMO

Vaccination has been regarded as the most effective way to reduce death and morbidity caused by infectious diseases in the livestock industry. In this study, plasma activated water (PAW) was introduced to prepare the inactivated Newcastle disease vaccine. Humoral immune response was tested by hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). In addition, cell-mediated immune response was evaluated by lymphocyte proliferation assay and flow cytometry. The results demonstrated that the vaccine prepared by PAW at appropriate volume ratio could induce similar antibody titers in specific pathogen-free (SPF) chickens compared with the formaldehyde-inactivated vaccine. The challenge experiment further confirmed that the vaccine prepared by PAW conferred solid protection against virulent NDV. Moreover, it was found that the vaccine could promote the proliferation of lymphocytes and stimulate cell-mediated immunity of SPF chickens. Furthermore, analysis of electron spin resonance (ESR) spectroscopy and physicochemical properties of PAW suggested reactive oxygen and nitrogen species (RONS) played an essential role in the virus inactivation. Therefore, this study indicated that NDV treated by PAW in an appropriate ratio retained immunogenicity on the premise of virus inactivation. PAW as a promising strategy could be used to prepare inactivated vaccine for Newcastle disease.


Assuntos
Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Gases em Plasma/química , Vacinas Virais/imunologia , Água/análise , Animais , Anticorpos Antivirais/sangue , Galinhas/imunologia , Testes de Inibição da Hemaglutinação , Imunidade Celular , Imunidade Humoral , Ativação Linfocitária , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Vacinas de Produtos Inativados , Vacinas Virais/administração & dosagem
18.
J Appl Anim Welf Sci ; 23(1): 95-107, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31296055

RESUMO

A total of 416 day-old ostrich chicks were randomly allocated to one of the three different husbandry practices for 3 months after hatch; HP1 (extensive human presence with gentle human voice, visual and gentle physical stimuli), HP2 (similar to HP1 but without physical stimuli) and S (human presence limited to supply of feed and water). Chick weight (kg) was measured at 6 and 12 weeks of age, while mortalities were recorded daily to calculate the survival rate. Finally, chicks' antibody responses to vaccination against Newcastle disease (NCD) was measured using the Hemagglutination-Inhibition (HI) test at 20 weeks of age. While HP1 chicks were heavier and survived better to 6 weeks of age than HP2 and S chicks (p < .05), no difference was observed thereafter (p > .05). Furthermore, HP1 chicks had an improved immune competence, as illustrated by their lower percentage of positive HI titers, compared to HP2 and S chicks (p < .05). Hence, integrating extensive human presence with positive human-chick interactions may assist in alleviating challenges related to chick rearing in the ostrich industry.


Assuntos
Criação de Animais Domésticos/métodos , Struthioniformes/crescimento & desenvolvimento , Struthioniformes/imunologia , Animais , Animais Recém-Nascidos , Feminino , Humanos , Masculino , Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinação/veterinária , Vacinas Virais/imunologia
19.
Biologicals ; 63: 74-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753578

RESUMO

The traditional vaccine strains, such as LaSota, do not completely prevent the shedding of NDV. An ideal vaccine which could not only prevent the clinical signs, but significantly reduce the shedding of NDV is urgently needed for the eradication of ND. In this study, an NDV isolate APMV-1/Chicken/China (SC)/PT3/2016 (hereafter referred as PT3) was identified as a class Ⅰ NDV and a lentogenic strain. The antigenic relationship between PT3 and 3 other NDV strains, including vaccine strain LaSota and 2 prevalent genotype Ⅶd and Ⅵb strains were analyzed. The protective efficacy of PT3 and LaSota against challenge with genotype Ⅶd and Ⅵb strains were assessed. The antigenic analysis result showed that 4 strains belong to the single serotype and the PT3 antiserum exhibited the highest HI titer against 3 other NDV strains. The results of protective efficacy showed that both of LaSota and PT3 could provide 100% survivability for infected chickens. However, PT3 performed better in inducing higher humoral responses and reducing virus shedding than the LaSota strain. Lentogenic strains from Class I NDV appear to be promising vaccine candidates for the control of ND, and allows for the easy discrimination of field NDV and vaccine strains.


Assuntos
Doença de Newcastle/prevenção & controle , Vírus da Doença de Newcastle/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Proteínas Aviárias/imunologia , Galinhas , Doença de Newcastle/imunologia , Doença de Newcastle/patologia , Vírus da Doença de Newcastle/classificação , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/patologia
20.
Int J Cancer ; 146(2): 531-541, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31584185

RESUMO

We have developed an oncolytic Newcastle disease virus (NDV) that has potent in vitro and in vivo anti-tumor activities and attenuated pathogenicity in chickens. In this ex vivo study using the same recombinant NDV backbone with GFP transgene (NDV-GFP, designated as rNDV), we found that rNDV induces maturation of monocyte-derived immature dendritic cells (iDCs) by both direct and indirect mechanisms, which promote development of antigen-specific T cell responses. Addition of rNDV directly to iDCs culture induced DC maturation, as demonstrated by the increased expression of costimulatory and antigen-presenting molecules as well as the production of type I interferons (IFNs). rNDV infection of the HER-2 positive human breast cancer cell line (SKBR3) resulted in apoptotic cell death, release of proinflammatory cytokines, and danger-associated molecular pattern molecules (DAMPs) including high-mobility group protein B1 (HMGB1) and heat shock protein 70 (HSP70). Addition of rNDV-infected SKBR3 cells to iDC culture resulted in greatly enhanced upregulation of the maturation markers and release of type I IFNs by DCs than rNDV-infected DCs only. When co-cultured with autologous T cells, DCs pre-treated with rNDV-infected SKBR3 cells cross-primed T cells in an antigen-specific manner. Altogether, our data strongly support the potential of oncolytic NDV as efficient therapeutic agent for cancer treatment.


Assuntos
Apresentação Cruzada , Células Dendríticas/imunologia , Imunoterapia/métodos , Neoplasias/terapia , Terapia Viral Oncolítica/métodos , Animais , Chlorocebus aethiops , Técnicas de Cocultura , Células Dendríticas/metabolismo , Feminino , Células HeLa , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Neoplasias/imunologia , Vírus da Doença de Newcastle/genética , Vírus da Doença de Newcastle/imunologia , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , RNA/administração & dosagem , RNA/genética , RNA Viral/administração & dosagem , RNA Viral/genética , Linfócitos T/imunologia , Células Vero
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