Showing papers on "Newcastle disease published in 2020"
13 Jan 2020
TL;DR: In this paper, the authors provide a detailed coverage of the history, etiology, pathobiology, epidemiology, diagnosis, and intervention strategies of Newcastle disease, APMV, and avian Metapneumovirus Infections.
Abstract: The Paramyxoviridae family has several genera that include important human and veterinary pathogens such as Rubulavirus, Respiroviruses, Henipavirus, and the Avulavirus genus that contains Newcastle disease virus (NDV) and other avian paramyxoviruses (APMV). This chapter focuses on infections of poultry with NDV. It offers detailed coverage of the history, etiology, pathobiology, epidemiology, diagnosis, and intervention strategies of Newcastle disease, APMV, and avian Metapneumovirus Infections. AMPV infections continue to emerge as a disease threat with four defined subtypes, A-D, being recognized and producing clinical disease in both turkeys and chickens. For effective disease management, it is important to be able to identify birds that are infected with NDV and distinguish vaccine viruses from virulent viruses. Regardless of whether ND control is applied at the international, national, or farm level, the objective is either to prevent susceptible birds from becoming infected or to reduce the number of susceptible birds by vaccination.
117 citations
TL;DR: It is reported that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly in mice, and these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs.
72 citations
TL;DR: Pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent coronavirus disease 2019 (COVID-19) vaccine in mice and hamsters suggest antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.
66 citations
TL;DR: Pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters show immunogenic results and suggest antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.
Abstract: A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.
28 citations
TL;DR: PAW as a promising strategy could be used to prepare inactivated vaccine for Newcastle disease and indicated that NDV treated by PAW in an appropriate ratio retained immunogenicity on the premise of virus inactivation.
Abstract: 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.
26 citations
TL;DR: Results indicate that the NDV-vectored FAdV-4 vaccine is a promising bivalent vaccine candidate to control both HHS and ND.
23 citations
TL;DR: An insight is provided of the recently emerging IBV outbreaks in IBV‐vaccinated commercial poultry farms and the genetic characteristics of three virulent GI‐19 IBV strains are identified, which shows the need to carry out proper preventive measures and control strategies.
Abstract: Infectious bronchitis virus (IBV), an ongoing emergence enveloped virus with a single-stranded positive-sense RNA genome, belongs to the Gammacoronavirus genus in the Coronaviridae family. IBV-associated tracheitis, nephritis, salpingitis, proventriculitis and egg drop have caused devastating economic losses to poultry industry worldwide. Since the end of 2018, a remarkably increasing number of commercial broilers and layers, vaccinated or not, were infected with IBV in China. Here, we described two IB outbreaks with severe respiratory system or kidney injury in IBV-vaccinated commercial poultry farms in central China. Other possible causative viral pathogens, including avian influenza virus (AIV), Newcastle disease virus (NDV) and Kedah fatal kidney syndrome virus (KFKSV), were excluded by reverse transcription-polymerase chain reaction (RT-PCR), and three virulent IBV strains, HeN-1/China/2019, HeN-2/China/2019 and HeN-101/China/2019, were identified. Although the gross pathologic appearance of these two IB outbreaks was different, the newly identified IBV strains were all closely related to the ck/China/I0529/17 strain and grouped into GI-19 genotype clade based on the sequencing and phylogenetic analysis of the complete S1 genes. Moreover, there are still some evolutionary distance between the newly identified IBV strains, HeN-101/China/2019 in particular, and other GI-19 strains, suggesting that Chinese IBV strains constantly emerge and evolve towards different directions. In conclusion, this study provided an insight of the recently emerging IBV outbreaks in IBV-vaccinated commercial poultry farms and identified the genetic characteristics of three virulent GI-19 IBV strains, which shows the need to carry out proper preventive measures and control strategies.
23 citations
TL;DR: It is shown that anti-IL-1β neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV, and inhibition of IL-1 β via anti-il-1α neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL- 1β expression via NLRP3/caspase-1.
Abstract: Newcastle disease virus (NDV) infection causes severe inflammation and is a highly contagious disease in poultry. Virulent NDV strains (GM) induce large quantities of interleukin-1β (IL-1β), which is the central mediator of the inflammatory reaction. Excessive expression of IL-1β exacerbates inflammatory damage. Therefore, exploring the mechanisms underlying NDV-induced IL-1β expression can aid in further understanding the pathogenesis of Newcastle disease. Here, we showed that anti-IL-1β neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV. We further explored the primary molecules involved in NDV-induced IL-1β expression from the perspective of both the host and virus. This study showed that overexpression of NLRP3 resulted in increased IL-1β expression, whereas inhibition of NLRP3 or caspase-1 caused a significant reduction in IL-1β expression, indicating that the NLRP3/caspase-1 axis is involved in NDV-induced IL-1β expression. Moreover, ultraviolet-inactivated GM (chicken/Guangdong/GM/2014) NDV failed to induce the expression of IL-1β. We then collected virus from GM-infected cell culture supernatant using ultracentrifugation, extracted the viral RNA, and stimulated the cells further with GM RNA. The results revealed that RNA alone was capable of inducing IL-1β expression. Moreover, NLRP3/caspase-1 was involved in GM RNA-induced IL-1β expression. Thus, our study elucidated the critical role of IL-1β in the pathogenesis of Newcastle disease while also demonstrating that inhibition of IL-1β via anti-IL-1β neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL-1β expression via NLRP3/caspase-1.
22 citations
TL;DR: Essential oils showed an antiviral effect on vNDv in vivo (in chickens) as a preventive measure as well as some therapeutic effect (TTT) through decreasing the viral shedding titres, mortality rate, and severity of clinical signs and post mortem lesions, in addition to serum malondialdhyde (MDA) level.
21 citations
TL;DR: It is indicated 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.
17 citations
DOI•
15 Jun 2020
TL;DR: The preparation of inactivated oil adjuvant vaccine from NDV field circulating strains was efficient in controlling the disease in Egypt, while the unadjuvanted vaccine could not provide any protective efficiency.
Abstract: Newcastle disease (ND) causes severe economic losses in poultry production Despite the intensive vaccination regimes of NDV in Egypt, many outbreaks are being reported The present study focused on the preparation and evaluation of inactivated velogenic Newcastle disease virus vaccine (genotype VII) isolated from Egyptian broiler chicken during 2015-2016 Fifty-five tissue samples including trachea, lung, liver, proventriculus, intestine, and kidney collected from commercial broiler chickens were used for virus isolation in specific pathogen-free embryonated chicken eggs (ECE) and identified using RT-PCR and sequencing The isolates were classified by sequencing as velogenic NDV genotype VIId containing F0 protein cleavage site motifs (112RRQKRF117) A selected isolate was served as a master seed for the preparation of inactivated NDV vaccine with or without Montanide ISA70 adjuvant and evaluated in SPF chicks Nine NDV isolates were isolated on ECE and the highest infectivity titer of the virus was 750 log10 EID50 mL-1 by the 5th passage Vaccinated chicks with NDV-Montanide ISA70 adjuvanted vaccine exhibited antibody titer of 520 log2 at the 3rd-week-post-vaccination (WPV) with the highest titer (890 log2 mL-1) at the 6th-WPV Protective antibodies values were persisted to 12th WPV followed by a gradual decrease to the end of the experiment (16th weeks) Vaccination of chicks with inactivated NDV isolate without adjuvant failed to induce protective HI antibodies all over the experiment Chickens vaccinated with the ISA70 adjuvant vaccine were passed homologous challenge tests with 100% protective efficiency, while the unadjuvanted vaccine could not provide any protective efficiency In conclusion, the preparation of inactivated oil adjuvant vaccine from NDV field circulating strains was efficient in controlling the disease in Egypt
TL;DR: It is suggested 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 dose (2 doses).
TL;DR: Dietary omega-3 supplementation for 4 weeks can improve growth performance and alleviate the deleterious immunological and pathological effects of NDV and AIV H9N2 infection in quails.
Abstract: This study was performed to evaluate the effects of omega-3 supplementation on growth performance, clinical signs, post-mortem lesions, haemagglutination inhibition (HI) antibody titres, gene expression and histopathology in quails (Coturnix coturnix japonica) infected with Newcastle disease virus (NDV) and avian influenza virus (AIV) H9N2. One hundred, 40-day-old male quails were divided into 5 groups: G1, fed a control basal diet; G2A, infected with NDV; G2B, infected with H9N2; G3A, infected with NDV and given omega-3, and G3B, infected with H9N2 and given omega-3. The dietary omega-3 supplementation was continued for 4 weeks: two weeks before infection and two weeks after intranasal infection with virulent NDV and AIV H9N2. Our results revealed significant differences (P < 0.05) in growth performance, HI antibody titres, clinical signs, post-mortem lesions, mortality, viral shedding rates, immunological parameters, and histopathological lesions between the treated (G3A and G3B) and untreated (G2A and G2B) groups. In conclusion, dietary omega-3 supplementation for 4 weeks can improve growth performance and alleviate the deleterious immunological and pathological effects of NDV and AIV H9N2 infection in quails.
TL;DR: By jointly analyzing the three tissues, this study identified genes and gene networks that led to a more comprehensive understanding of the whole animal response to lentogenic NDV than that obtained by analyzing the tissues individually.
Abstract: Disease has large negative impacts on poultry production. A more comprehensive understanding of host-pathogen interaction can lead to new and improved strategies to maintain health. In particular, host genetic factors can lead to a more effective response to pathogens, hereafter termed resistance. Fayoumi and Leghorn chicken lines have demonstrated relative resistance and susceptibility, respectively, to the Newcastle disease virus (NDV) vaccine strain and many other pathogens. This biological model was used to better understand the host response to a vaccine strain of NDV across three tissues and time points, using RNA-seq. Analyzing the Harderian gland, trachea, and lung tissues together using weighted gene co-expression network analysis (WGCNA) identified important genes that were co-expressed and associated with parameters including: genetic line, days post-infection (dpi), challenge status, sex, and tissue. Pathways and driver genes, such as EIF2AK2, MPEG1, and TNFSF13B, associated with challenge status, dpi, and genetic line were of particular interest as candidates for disease resistance. Overall, by jointly analyzing the three tissues, this study identified genes and gene networks that led to a more comprehensive understanding of the whole animal response to lentogenic NDV than that obtained by analyzing the tissues individually.
TL;DR: The results indicated that the reverse transcription recombinase-aided amplification assay may be a valuable tool for detecting avian influenza H7 subtype virus.
Abstract: H7 subtype avian influenza virus infection is an emerging zoonosis in some Asian countries and an important avian disease worldwide A rapid and simple test is needed to confirm infection in suspected cases during disease outbreaks In this study, we developed a reverse-transcription recombinase-aided amplification assay for the detection of H7 subtype avian influenza virus Assays were performed at a single temperature (39degreesC), and the results were obtained within 20 min The assay showed no cross-detection with Newcastle disease virus or infectious bronchitis virus, which are the other main respiratory viruses affecting birds The analytical sensitivity was 10sup2/sup RNA copies per reaction at a 95% probability level according to probit regression analysis, with 100% specificity Compared with published reverse-transcription quantitative real-time polymerase chain reaction assays, the kappa value of the reverse-transcription recombinase-aided amplification assay in 342 avian clinical samples was 0 988 (p 001) The sensitivity for avian clinical sample detection was 100% (95%CI, 90 40%-100%), and the specificity was 99 96% (95%CI, 97 83%-99 98%) These results indicated that our reverse-transcription recombinase-aided amplification assay may be a valuable tool for detecting avian influenza H7 subtype virus
TL;DR: Findings collectively indicate that mIBS025 provides a better protective efficacy than LaSota and therefore can be used as a promising vaccine candidate against genotype VII NDV strains.
TL;DR: The complete genomes of 18 PPMV-1 isolated in China during 2012–2018 were sequenced by next-generation sequencing (NGS) and comprehensive phylogenetic analyses showed that five of the viruses belong to sub-genotype VI1.2.1.1 and 13 isolates belong toSub-genotypes VI have been predominant inChina during the last decade.
Abstract: Newcastle disease is an important poultry disease that also affects Columbiform birds. The viruses adapted to pigeons and doves are referred to as pigeon paramyxoviruses 1 (PPMV-1). PPMV-1 are frequently isolated from pigeons worldwide and have the potential to cause disease in chickens. The complete genomes of 18 PPMV-1 isolated in China during 2012-2018 were sequenced by next-generation sequencing (NGS). Comprehensive phylogenetic analyses showed that five of the viruses belong to sub-genotype VI1.2.1.1.2.1 and 13 isolates belong to sub-genotype VI.2.1.1.2.2. The results demonstrate that these sub-genotypes have been predominant in China during the last decade. The viruses of these sub-genotypes have been independently maintained and continuously evolved for over 20 years, and differ significantly from those causing outbreaks worldwide during the 1980s to 2010s. The viral reservoir remains unknown and possibilities of the viruses being maintained in both pigeon farms and wild bird populations are viable. In vivo characterization of the isolates' pathogenicity estimated mean death times between 62 and 114 hours and intracerebral pathogenicity indices between 0.00 and 0.63. Cross-reactivity testing showed minor antigenic differences between the studied viruses and the genotype II LaSota vaccine. These data will facilitate PPMV-1 epidemiology studies, vaccine development, and control of Newcastle disease in pigeons and poultry.
TL;DR: The combination of recombinant rHVT ND-IBD with a live vaccine at one-day-old seems to be a better combination, due to the absence of clinical signs, higher antibody levels pre and post-challenge, and reduced virus shedding at any time point after the challenge at 3 or 4 weeks of age with the California 2018 virus.
TL;DR: The materials and methods involved in the in vitro cloning and rescue of NDV expressing murine 4-1BBL as well as the in vivo evaluation ofNDV expressing 4- 1BBL in a B16-F10 murine melanoma model are described.
Abstract: Newcastle disease virus (NDV) is an avian paramyxovirus that has been extensively studied as an oncolytic agent, in addition to being an economically important pathogen in the poultry industry. The establishment of a reverse genetics system for this virus has enabled the development of genetically modified recombinant NDV viruses with improved oncolytic and immunotherapeutic properties. In this chapter, we describe the materials and methods involved in the in vitro cloning and rescue of NDV expressing murine 4-1BBL as well as the in vivo evaluation of NDV expressing 4-1BBL in a B16-F10 murine melanoma model.
TL;DR: It was discovered that the novel variant IBDV could interfere with ND vaccination in both broilers and layers, which was one important factor involved in immune failure in poultry farms, and suggests the urgency to control the novel variants IBDv infection for healthy breeding.
TL;DR: The detection of anti-NDV antibodies in the sera of chickens that were fed maize with immunogenic protein, and the absence of these antibodies in chickens fed a normal diet, confirmed the specificity of the antibodies generated through feeding, and demonstrated the potential of utilizing plants for producing more vaccine doses, vaccine generation at higher levels and against other infectious diseases.
Abstract: Newcastle disease (ND) is a viral disease that causes labored breathing, periorbital oedema, and ataxia in the majority of avian species. The available vaccines against Newcastle disease virus (NDV) are limited, owing to their low reactivity and multiple dosage requirements. Plant-based machinery provides an attractive and safe system for vaccine production. In the current study, we attempted to express fusion (F) and hemagglutinin-neuraminidase (HN) proteins (the protective antigens against NDV) under constitutive 35S and seed-specific Zein promoters, respectively. Almost 2-7.1-fold higher expression of F gene mRNA in transgenic corn leaves and 8-28-fold higher expression of HN gene mRNA in transgenic corn seeds were observed, when the expression was analyzed by real-time PCR on a relative basis as compared to non-transgenic control plant material (Leaves and seeds). Similarly, 1.66 μg/ml of F protein in corn leaves, i.e., 0.5% of total soluble protein, and 2.4 μg/ml of HN protein in corn seed, i.e., 0.8% of total seed protein, were found when calculated through ELISA. Similar levels of immunological response were generated in chicks immunized through injection of E. coli-produced pET F and pET HN protein as in chickens orally fed leaves and seeds of maize with expressed immunogenic protein. Moreover, the detection of anti-NDV antibodies in the sera of chickens that were fed maize with immunogenic protein, and the absence of these antibodies in chickens fed a normal diet, confirmed the specificity of the antibodies generated through feeding, and demonstrated the potential of utilizing plants for producing more vaccine doses, vaccine generation at higher levels and against other infectious diseases.
TL;DR: L. acidophilus can use for improving immunogenicity of NDV vaccination programs, and antibody levels against NDV increased during the vaccination period especially in probiotic treated groups.
Abstract: Introduction and purpose Despite the various vaccination programs for protection against New Castle disease, it remains an important threat to the poultry industry. The ability of the probiotic bacteria to improve the immune system in both animals and humans supports their use as immune adjuvants for vaccination. The aim of the present study was to examine the effects of Lactobacillus acidophilus in ND vaccination. Materials and methods A total of 170 one day old chicks were divided in 5 groups. In groups A, B and C chicks were received L. acidophilus (5 × 109, 3 × 109 and 2 × 109) and also vaccinated with inactivated and attenuated ND vaccines. In group D, chicks only vaccinated without bacterial inoculation and group E was negative control with neither vaccine nor bacteria. Then IgG and HI NDV antibody titers were measured in all tested groups. Results IgG and HI NDV antibody levels were significantly higher in Lactobacillus treated groups especially in group A with 5 × 109 bacteria, than only vaccinated and negative control groups. Also antibody levels against NDV increased during the vaccination period especially in probiotic treated groups. Conclusion In conclusion, L. acidophilus can use for improving immunogenicity of NDV vaccination programs.
TL;DR: It is demonstrated in a proof-of-concept study that an NDV vectored vaccine can protect against PPR and provides DIVA-applicability and a high thermal tolerance.
TL;DR: It was shown that inactivated poultry vaccines stimulated nitric oxide production and Fc receptor-mediated phagocytosis by chicken macrophages, and the cell-based assays described here can be used for future assessment of vaccine batch-to-batch consistency.
TL;DR: The results demonstrate that the plant-derived F vaccine along with immunochromatographic strips could be useful in the implementation of an NDV eradication program.
TL;DR: Avian paramyxovirus serotype 3 (APMV-3) strain Netherlands is evaluated as a safe vaccine vector against HPAIV, which has high efficiency replication in a greater range of host organs.
Abstract: Highly pathogenic avian influenza (HPAI) is a devastating disease of poultry and a serious threat to public health. Vaccination with inactivated virus vaccines has been applied for several years as one of the major policies to control highly pathogenic avian influenza virus (HPAIV) infections in chickens. Viral-vectored HA protein vaccines are a desirable alternative for inactivated vaccines. However, each viral vector possesses its own advantages and disadvantages for the development of a HA-based vaccine against HPAIV. Recombinant Newcastle disease virus (rNDV) strain LaSota expressing HA protein vaccine has shown promising results against HPAIV; however, its replication is restricted only to the respiratory tract. Therefore, we thought to evaluate avian paramyxovirus serotype 3 (APMV-3) strain Netherlands as a safe vaccine vector against HPAIV, which has high efficiency replication in a greater range of host organs. In this study, we generated rAPMV-3 expressing the HA protein of H5N1 HPAIV using reverse genetics and evaluated the induction of neutralizing antibodies and protection by rAPMV3 and rNDV expressing the HA protein against HPAIV challenge in chickens. Our results showed that immunization of chickens with rAPMV-3 or rNDV expressing HA protein provided complete protection against HPAIV challenge. However, immunization of chickens with rAPMV-3 expressing HA protein induced higher level of neutralizing antibodies compared to that of rNDV expressing HA protein. These results suggest that a rAPMV-3 expressing HA protein might be a better vaccine for mass-vaccination of commercial chickens in field conditions.
TL;DR: The colloidal gold test strip showed high specificity in the detection of ILTV, with no cross-reaction with other avian pathogens, including infectious bronchitis virus, infectious bursal disease virus, avian influenza virus, Newcastle disease virus and fowl adenoviruses.
TL;DR: It is suggested that interaction of HA1 and HA2 subunits is necessary for the display of epitopes on HA protein involved in the induction of neutralizing antibodies and protection against HPAIV, and vaccination with either a HA1 orHA2 subunit may not provide protection against the virus.
Abstract: Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes a devastating disease in poultry. Vaccination is an effective method of controlling avian influenza virus (AIV) infection in poultry. The hemagglutinin (HA) protein is the major determinant recognized by the immune system of the host. Cleavage of the HA precursor HA0 into HA1 and HA2 subunits is required for infectivity of the AIV. We evaluated the individual contributions of HA1 and HA2 subunits to the induction of HPAIV serum neutralizing antibodies and protective immunity in chickens. Using reverse genetics, recombinant Newcastle disease viruses (rNDVs) were generated, each expressing HA1, HA2, or HA protein of H5N1 HPAIV. Chickens were immunized with rNDVs expressing HA1, HA2, or HA. Immunization with HA induced high titers of serum neutralizing antibodies and prevented death following challenge. Immunization with HA1 or HA2 alone neither induced serum neutralizing antibodies nor prevented death following challenge. Our results suggest that interaction of HA1 and HA2 subunits is necessary for the display of epitopes on HA protein involved in the induction of neutralizing antibodies and protection. These epitopes are lost when the two subunits are separated. Therefore, vaccination with either a HA1 or HA2 subunit may not provide protection against HPAIV.
TL;DR: In this article, a chicken A4 (chA4) mRNA was identified and cloned for the first time, and the conserved zinc-coordinating motif (HXE … PC(X)2-6C) was identified on the surface of chA4 and contained highly conserved His97, Glu99, Pro130, Cys131 and Cys138 active sites.
Abstract: The APOBEC proteins play significant roles in the innate and adaptive immune system, probably due to their deaminase activities. Because APOBEC1 (A1) and APOBEC3 (A3) are absent in the chicken genome, we were interested in determining whether chicken APOBEC4 (A4) possessed more complex functions than its mammalian homologs. In this study, chicken A4 (chA4) mRNA was identified and cloned for the first time. Based on bioinformatics analyses, the conserved zinc-coordinating motif (HXE … PC(X)2-6C) was identified on the surface of chA4 and contained highly conserved His97, Glu99, Pro130, Cys131 and Cys138 active sites. The highest expression levels of constitutive chA4 were detected in primary lymphocytes and bursa of Fabricius. Newcastle Disease (ND) is one of the most serious infectious diseases in birds, causing major economic losses to the poultry industry. In vitro, Newcastle Disease Virus (NDV) early infection induced significant increases in chA4 expression in the chicken B cell line, DT40, the macrophage cell line, HD11 and the CD4+ T cell line, MSB-1, but not the fibroblast cell line, DF-1. In vivo, the expression levels of chA4 were up-regulated in several tissues from NDV-infected chickens, especially the thymus, testicles, duodenum and kidney. The high level expression of exogenous chA4 displayed inhibitory effects on NDV and reduced viral RNA in infected cells. Taken together, these data demonstrate that chA4 is involved in the chicken immune system and may play important roles in host anti-viral responses.
TL;DR: Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format are described and it is reported that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly.
Abstract: Due to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs.