scholarly journals The recombinant pseudorabies virus expressing porcine deltacoronavirus spike protein is safe and effective for mice

2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Yao Huang ◽  
Zhiwen Xu ◽  
Sirui Gu ◽  
Mincai Nie ◽  
Yuling Wang ◽  
...  
Keyword(s):  
Antibody Level ◽  
Recombinant Strain ◽  
Gene Editing ◽  
Pseudorabies Virus ◽  
Virulent Strain ◽  
Neutralizing Antibody ◽  
Economic Loss ◽  
Recombinant Pseudorabies Virus ◽  
Ifn Γ ◽  
Significant Economic Loss

Abstract Background Porcine deltacoronavirus (PDCoV) is a new pathogenic porcine intestinal coronavirus, which has appeared in many countries since 2012. PDCoV disease caused acute diarrhea, vomiting, dehydration and death in piglets, resulted in significant economic loss to the pig industry. However, there is no commercially available vaccine for PDCoV. In this study, we constructed recombinant pseudorabies virus (rPRVXJ-delgE/gI/TK-S) expressing PDCoV spike (S) protein and evaluated its safety and immunogenicity in mice. Results The recombinant strain rPRVXJ-delgE/gI/TK-S obtained by CRISPR/Cas gE gene editing technology and homologous recombination technology has genetic stability in baby hamster syrian kidney-21 (BHK-21) cells and is safe to mice. After immunizing mice with rPRVXJ-delgE/gI/TK-S, the expression levels of IFN-γ and IL-4 in peripheral blood of mice were up-regulated, the proliferation of spleen-specific T lymphocytes and the percentage of CD4+ and CD8+ lymphocytes in mice spleen was increased. rPRVXJ-delgE/gI/TK-S showed good immunogenicity for mice. On the seventh day after booster immunity, PRV gB and PDCoV S specific antibodies were detected in mice, and the antibody level continued to increase, and the neutralizing antibody level reached the maximum at 28 days post- immunization (dpi). The recombinant strain can protect mice with 100% from the challenge of virulent strain (PRV XJ) and accelerate the detoxification of PDCoV in mice. Conclusion The recombinant rPRVXJ-delgE/gI/TK-S strain is safe and effective with strong immunogenicity and is expected to be a candidate vaccine against PDCoV and PRV.

scholarly journals The recombinant pseudorabies virus expressing African swine fever virus CD2v protein is safe and effective in mice

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Zhihua Feng ◽  
Jianghua Chen ◽  
Wangwang Liang ◽  
Wenzhi Chen ◽  
Zhaolong Li ◽  
...  
Keyword(s):  
Recombinant Virus ◽  
Recombinant Strain ◽  
Pseudorabies Virus ◽  
Vaccine Candidate ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Vero Cells ◽  
Fever Virus ◽  
Virus Vaccination ◽  
Recombinant Pseudorabies Virus

Abstract Background African swine fever (ASF) leads to high mortality in domestic pigs and wild boar and is caused by the African swine fever virus (ASFV). Currently, no vaccine is commercially available for prevention, and the epidemic is still spreading. Here, we constructed a recombinant pseudorabies virus (PRV) (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) that expresses the CD2v protein of ASFV and evaluated its effectiveness and safety as a vaccine candidate in mice. Methods A homologous recombination fragment containing ASFV CD2v was synthesized and co-transfected into HEK 293 T cells, a knockout vector targeting the PRV TK gene. The transfected cells were infected with PRV-ΔgE/ΔgI, and the recombinant strain (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) was obtained by plaque purification in Vero cells. The expression of ASFV CD2v in the recombinant virus was confirmed by sequencing, Western blotting, and immunofluorescence analysis, and the genetic stability was tested in Vero cells over 20 passages. The virulence, immunogenicity and protective ability of the recombinant virus were further tested in a mouse model. Results The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain is stable in Vero cells, and the processing of CD2v does not depend on ASFV infection. The vaccination of PRV-ΔgE/ΔgI/ΔTK-(CD2v) causes neither pruritus, not a systemic infection and inflammation (with the high expression of interleukin-6 (IL6)). Besides, the virus vaccination can produce anti-CD2v specific antibody and activate a specific cellular immune response, and 100% protect mice from the challenge of the virulent strain (PRV-Fa). The detoxification occurs much earlier upon the recombinant virus vaccination and the amount of detoxification is much lower as well. Conclusions The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain has strong immunogenicity, is safe and effective, and maybe a potential vaccine candidate for the prevention of ASF and Pseudorabies.

scholarly journals Evaluation of the Efficacy of a Cholera Toxin-Based Staphylococcus aureus Vaccine against Bovine Intramammary Challenge

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 6
Author(s):  
Hussain A. Alabdullah ◽  
Elise Overgaard ◽  
Danielle Scarbrough ◽  
Janet E. Williams ◽  
Omid Mohammad Mousa ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cholera Toxin ◽  
Bovine Mastitis ◽  
Economic Loss ◽  
B Subunit ◽  
Specific Immunoglobulin ◽  
Ifn Γ ◽  
And Control ◽  
Primary Agent ◽  
Significant Economic Loss

Staphylococcus aureus (S. aureus) is a primary agent of bovine mastitis and a source of significant economic loss for the dairy industry. We previously reported antigen-specific immune induction in the milk and serum of dairy cows following vaccination with a cholera toxin A2 and B subunit (CTA2/B) based vaccine containing the iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) antigens of S. aureus (IsdA + ClfA-CTA2/B). The goal of the current study was to assess the efficacy of this vaccine to protect against S. aureus infection after intramammary challenge. Six mid-lactation heifers were randomized to vaccinated and control groups. On days 1 and 14 animals were inoculated intranasally with vaccine or vehicle control, and on day 20 animals were challenged with S. aureus. Clinical outcome, milk quality, bacterial shedding, and somatic cell count (SCC) were followed for ten days post-challenge. Vaccinated animals did not show signs of clinical S. aureus mastitis and had lower SCCs compared to control animals during the challenge period. Reductions in bacterial shedding were observed but were not significant between groups. Antibody analysis of milk and serum indicated that, upon challenge, vaccinated animals produced enhanced IsdA- and ClfA-CTA2/B specific immunoglobulin G (IgG) responses, while responses to CTA2/B alone were not different between groups. Responses after challenge were largely IgG1 against the IsdA antigen and mixed IgG1/IgG2 against the ClfA antigen. In addition, there was a significant increase in interferon gamma (IFN-γ) expression from blood cells in vaccinated animals on day 20. While preliminary, these findings support evidence of the induction of active immunity by IsdA + ClfA-CTA2/B, and further assessment of this vaccine is warranted.

scholarly journals PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Zongyi Bo ◽  
Yurun Miao ◽  
Rui Xi ◽  
Qiuping Zhong ◽  
Chenyi Bao ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Pseudorabies Virus ◽  
Nuclear Translocation ◽  
Economic Loss ◽  
Inhibitory Effect ◽  
Poly I:C ◽  
Interferon Response ◽  
Type I ◽  
Creb Binding Protein ◽  
Swine Industry

Abstract Cyclic GMP-AMP (cGAMP) synthase (cGAS) is an intracellular sensor of cytoplasmic viral DNA created during virus infection, which subsequently activates the stimulator of interferon gene (STING)-dependent type I interferon response to eliminate pathogens. In contrast, viruses have developed different strategies to modulate this signalling pathway. Pseudorabies virus (PRV), an alphaherpesvirus, is the causative agent of Aujeszky’s disease (AD), a notable disease that causes substantial economic loss to the swine industry globally. Previous reports have shown that PRV infection induces cGAS-dependent IFN-β production, conversely hydrolysing cGAMP, a second messenger synthesized by cGAS, and attenuates PRV-induced IRF3 activation and IFN-β secretion. However, it is not clear whether PRV open reading frames (ORFs) modulate the cGAS–STING-IRF3 pathway. Here, 50 PRV ORFs were screened, showing that PRV UL13 serine/threonine kinase blocks the cGAS–STING-IRF3-, poly(I:C)- or VSV-mediated transcriptional activation of the IFN-β gene. Importantly, it was discovered that UL13 phosphorylates IRF3, and its kinase activity is indispensable for such an inhibitory effect. Moreover, UL13 does not affect IRF3 dimerization, nuclear translocation or association with CREB-binding protein (CBP) but attenuates the binding of IRF3 to the IRF3-responsive promoter. Consistent with this, it was discovered that UL13 inhibits the expression of multiple interferon-stimulated genes (ISGs) induced by cGAS–STING or poly(I:C). Finally, it was determined that PRV infection can activate IRF3 by recruiting it to the nucleus, and PRVΔUL13 mutants enhance the transactivation level of the IFN-β gene. Taken together, the data from the present study demonstrated that PRV UL13 inhibits cGAS–STING-mediated IFN-β production by phosphorylating IRF3.

scholarly journals Impact of Nisin and Nisin-Producing Lactococcus lactis ssp. lactis on Clostridium tyrobutyricum and Bacterial Ecosystem of Cheese Matrices

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 898
Author(s):  
Hebatoallah Hassan ◽  
Daniel St-Gelais ◽  
Ahmed Gomaa ◽  
Ismail Fliss
Keyword(s):  
Lactococcus Lactis ◽  
Cheddar Cheese ◽  
Economic Loss ◽  
Gas Production ◽  
Clostridium Tyrobutyricum ◽  
Nisin Production ◽  
Genus Clostridium ◽  
Milk Pasteurization ◽  
Cheese Slurry ◽  
Significant Economic Loss

Clostridium tyrobutyricum spores survive milk pasteurization and cause late blowing of cheeses and significant economic loss. The effectiveness of nisin-producing Lactococcus lactis ssp. lactis 32 as a protective strain for control the C. tyrobutyricum growth in Cheddar cheese slurry was compared to that of encapsulated nisin-A. The encapsulated nisin was more effective, with 1.0 log10 reductions of viable spores after one week at 30 °C and 4 °C. Spores were not detected for three weeks at 4 °C in cheese slurry made with 1.3% salt, or during week 2 with 2% salt. Gas production was observed after one week at 30 °C only in the control slurry made with 1.3% salt. In slurry made with the protective strain, the reduction in C. tyrobutyricum count was 0.6 log10 in the second week at 4 °C with both salt concentration. At 4 °C, nisin production started in week 2 and reached 97 µg/g after four weeks. Metabarcoding analysis targeting the sequencing of 16S rRNA revealed that the genus Lactococcus dominated for four weeks at 4 °C. In cheese slurry made with 2% salt, the relative abundance of the genus Clostridium decreased significantly in the presence of nisin or the protective strain. The results indicated that both strategies are able to control the growth of Clostridium development in Cheddar cheese slurries.

scholarly journals Rapid Multi-Hybridisation FISH Screening for Balanced Porcine Reciprocal Translocations Suggests a Much Higher Abnormality Rate Than Previously Appreciated

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 250
Author(s):  
Rebecca E O’Connor ◽  
Lucas G Kiazim ◽  
Claudia C Rathje ◽  
Rebecca L Jennings ◽  
Darren K Griffin
Keyword(s):  
Semen Analysis ◽  
In Situ Hybridisation ◽  
Economic Loss ◽  
Environmental Damage ◽  
Fluorescence In Situ Hybridisation ◽  
Reciprocal Translocations ◽  
Chromosome Translocations ◽  
Farrowing Rate ◽  
Significant Economic Loss

With demand rising, pigs are the world’s leading source of meat protein; however significant economic loss and environmental damage can be incurred if boars used for artificial insemination (AI) are hypoprolific (sub-fertile). Growing evidence suggests that semen analysis is an unreliable tool for diagnosing hypoprolificacy, with litter size and farrowing rate being more applicable. Once such data are available, however, any affected boar will have been in service for some time, with significant financial and environmental losses incurred. Reciprocal translocations (RTs) are the leading cause of porcine hypoprolificacy, reportedly present in 0.47% of AI boars. Traditional standard karyotyping, however, relies on animal specific expertise and does not detect more subtle (cryptic) translocations. Previously, we reported development of a multiple hybridisation fluorescence in situ hybridisation (FISH) strategy; here, we report on its use in 1641 AI boars. A total of 15 different RTs were identified in 69 boars, with four further animals XX/XY chimeric. Therefore, 4.5% had a chromosome abnormality (4.2% with an RT), a 0.88% incidence. Revisiting cases with both karyotype and FISH information, we reanalysed captured images, asking whether the translocation was detectable by karyotyping alone. The results suggest that chromosome translocations in boars may be significantly under-reported, thereby highlighting the need for pre-emptive screening by this method before a boar enters a breeding programme.

scholarly journals Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ismael Artur da Costa-Rocha ◽  
Ketty Lysie Libardi Lira Machado ◽  
Ana Carolina Campi-Azevedo ◽  
Andréa Teixeira-Carvalho ◽  
Vanessa Peruhype-Magalhães ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Neutralizing Antibody ◽  
Serum Biomarkers ◽  
Serum Biomarker ◽  
Time Points ◽  
Inflammatory Status ◽  
Biomarker Response ◽  
Ifn Γ ◽  
A Prospective Study

AbstractThe present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren’s Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3–4/D5–6/D7/D14–28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(−) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3–4/D5–6, the AID/PRNT(−) displayed higher response at later time points (D7/D14–D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5–6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(−) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(−). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

scholarly journals Efficacy of a Vaccine Based on Protective Antigen and Killed Spores against Experimental Inhalational Anthrax

2008 ◽  
Vol 77 (3) ◽  
pp. 1197-1207 ◽  
Author(s):  
Yves P. Gauthier ◽  
Jean-Nicolas Tournier ◽  
Jean-Charles Paucod ◽  
Jean-Philippe Corre ◽  
Michèle Mock ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Protective Immunity ◽  
Protective Antigen ◽  
Virulent Strain ◽  
Neutralizing Antibody ◽  
Cutaneous Anthrax ◽  
Anthrax Vaccines ◽  
Mucosal Secretions ◽  
Highly Virulent ◽  
Lethal Doses

ABSTRACTProtective antigen (PA)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so against inhalational anthrax. The aim of this work was to optimize immunization with PA-FIS and to assess vaccine efficacy against inhalational anthrax. We assessed the immune response to recombinant anthrax PA fromBacillus anthracis(rPA)-FIS administered by various immunization protocols and the protection provided to mice and guinea pigs infected through the respiratory route with spores of a virulent strain ofB. anthracis. Combined subcutaneous plus intranasal immunization of mice yielded a mucosal immunoglobulin G response to rPA that was more than 20 times higher than that in lung mucosal secretions after subcutaneous vaccination. The titers of toxin-neutralizing antibody and antispore antibody were also significantly higher: nine and eight times higher, respectively. The optimized immunization elicited total protection of mice intranasally infected with the virulentB. anthracisstrain 17JB. Guinea pigs were fully protected, both against an intranasal challenge with 100 50% lethal doses (LD50) and against an aerosol with 75 LD50of spores of the highly virulent strain 9602. Conversely, immunization with PA alone did not elicit protection. These results demonstrate that the association of PA and spores is very much more effective than PA alone against experimental inhalational anthrax.

Optimization of Thin-Film Winding Conditions Considering Viscoelastic Property and Thickness Variation and its Experimental Verification

2018 ◽  
Author(s):  
Yuta Sunami ◽  
Hiromu Hashimoto
Keyword(s):  
Viscoelastic Property ◽  
Stress Condition ◽  
Economic Loss ◽  
Thickness Variation ◽  
Plastic Films ◽  
Roll To Roll ◽  
Condition Optimization ◽  
Wound Rolls ◽  
Predicted Values ◽  
Significant Economic Loss

Plastic films are produced using roll-to-roll systems, which allow the film to be wound into a roll and stored in a small space. Roll defects, however, can cause significant economic loss, and gage bands remain an open area of research. More recently, plastic films have become thinner, so we must now reconsider wrinkling and slippage, problems which depend on the in-roll stress condition. Therefore, predicting the stress condition is essential to preventing defects occurring in wound rolls. In addition, the in-roll stress will change over time as a result of viscoelastic properties. This study theoretically investigates and experimentally verifies winding condition optimization and in-roll stress in consideration of the viscoelastic property and web thickness profile at a constant rewinding tension. Results show that the predicted values are in agreement with the measured values.

scholarly journals PREVALENCE OF BRUCELLOSIS IN BLACK BENGAL GOATS IN BANGLADESH

2013 ◽  
Vol 10 (1-2) ◽  
pp. 51-56 ◽  
Author(s):  
M. S. Rahman ◽  
S. Mithu ◽  
M. T. Islam ◽  
M. J. Uddin ◽  
R. R. Sarker ◽  
...  
Keyword(s):  
Epidemiological Data ◽  
Economic Loss ◽  
Cross Sectional Study ◽  
Confirmatory Test ◽  
Sectional Study ◽  
Cross Sectional ◽  
History Of ◽  
Significant Economic Loss ◽  
Sera Samples ◽  
Structured Questionnaire

Brucellosis is an important bacterial zoonotic disease causing significant economic loss in dairy industries worldwide including Bangladesh. But limited studies are devoted to determine the prevalence of brucellosis in goat in all districts of Bangladesh. Therefore, a cross-sectional study was undertaken to determine the seroprevalence of brucellosis in Black Bengal goats in Nilphamari Sadar and Kishoreganj upazillas of Nilphamari district of Bangladesh using Rose Bengal Test (RBT) as screening test and I-ELISA as confirmatory test. A total of 154 sera samples from Black Bengal goats were collected from Nilphamari district. Epidemiological data on the selected Black Bengal goats were collected using a structured questionnaire. The overall seroprevalence of brucellosis was found to be 2.59% in Black Bengal goats. A significantly (p<0.01) higher prevalence of brucellosis was found in Black Bengal goats with the history of previous abortion (33.33%). An insignificant (p>0.05) but higher prevalence of brucellosis was found in adult Black Bengal goats (>24 months) than young. The prevalence was relatively higher in cross-bred than pure Black Bengal goats, in female than male and in pregnant than non-pregnant Black Bengal goats. The result of the study will provide baseline data for control of brucellosis in goat in Bangladesh.DOI: http://dx.doi.org/10.3329/bjvm.v10i1-2.15646

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