scholarly journals The Bluetongue Disabled Infectious Single Animal (DISA) Vaccine Platform Based on Deletion NS3/NS3a Protein Is Safe and Protective in Cattle and Enables DIVA

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 857
Author(s):  
Piet A. van Rijn ◽  
Mieke A. Maris-Veldhuis ◽  
René G. P. van Gennip
Keyword(s):  
Control Measure ◽  
Outer Shell ◽  
Effective Control ◽  
Vaccine Platform ◽  
Virus Propagation ◽  
Biting Midges ◽  
Single Animal ◽  
Shell Proteins ◽  
Pros And Cons ◽  
Culicoides Biting Midges

The bluetongue virus (BTV) is transmitted by Culicoides biting midges and causes bluetongue (BT), an OIE-notifiable disease of ruminants. At least 29 BTV serotypes are described as determined by the outer shell proteins VP2 and VP5. Vaccination is the most effective control measure. Inactivated and live-attenuated vaccines (LAVs) are currently available. These vaccines have their specific pros and cons, and both are not DIVA vaccines. The BT Disabled Infectious Single Animal (DISA) vaccine platform is based on LAV without nonessential NS3/NS3a expression and is applicable for many serotypes by the exchange of outer shell proteins. The DISA vaccine is effective and completely safe. Further, transmission of the DISA vaccine by midges is blocked (DISA principle). Finally, the DISA vaccine enables DIVA because of a lack of antibodies against the immunogenic NS3/NS3a protein (DIVA principle). The deletion of 72 amino acids (72aa) in NS3/NS3a is sufficient to block virus propagation in midges. Here, we show that a prototype DISA vaccine based on LAV with the 72aa deletion enables DIVA, is completely safe and induces a long-lasting serotype-specific protection in cattle. In conclusion, the in-frame deletion of 72-aa codons in the BT DISA/DIVA vaccine platform is sufficient to fulfil all the criteria for modern veterinary vaccines.

scholarly journals Pentavalent Disabled Infectious Single Animal (DISA)/DIVA Vaccine Provides Protection in Sheep and Cattle against Different Serotypes of Bluetongue Virus

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1150
Author(s):  
Piet A. van Rijn ◽  
Mieke A. Maris-Veldhuis ◽  
Massimo Spedicato ◽  
Giovanni Savini ◽  
René G. P. van Gennip
Keyword(s):  
Bluetongue Virus ◽  
Control Measure ◽  
Genome Segment ◽  
Effective Control ◽  
Notifiable Disease ◽  
Vaccine Platform ◽  
Vp2 Protein ◽  
Single Animal ◽  
Pros And Cons ◽  
Ideal Vaccine

Bluetongue (BT) is a midge-borne OIE-notifiable disease of ruminants caused by the bluetongue virus (BTV). There are at least 29 BTV serotypes as determined by serum neutralization tests and genetic analyses of genome segment 2 encoding serotype immunodominant VP2 protein. Large parts of the world are endemic for multiple serotypes. The most effective control measure of BT is vaccination. Conventionally live-attenuated and inactivated BT vaccines are available but have their specific pros and cons and are not DIVA compatible. The prototype Disabled Infectious Single Animal (DISA)/DIVA vaccine based on knockout of NS3/NS3a protein of live-attenuated BTV, shortly named DISA8, fulfills all criteria for modern veterinary vaccines of sheep. Recently, DISA8 with an internal in-frame deletion of 72 amino acid codons in NS3/NS3a showed a similar ideal vaccine profile in cattle. Here, the DISA/DIVA vaccine platform was applied for other serotypes, and pentavalent DISA/DIVA vaccine for “European” serotypes 1, 2, 3, 4, 8 was studied in sheep and cattle. Protection was demonstrated for two serotypes, and neutralization Ab titers indicate protection against other included serotypes. The DISA/DIVA vaccine platform is flexible in use and generates monovalent and multivalent DISA vaccines to combat specific field situations with respect to Bluetongue.

scholarly journals Retrospective Analysis of the Bluetongue Outbreak in Serbia

2017 ◽  
Vol 40 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Spomenka Djurić ◽  
Predrag Simeunović ◽  
Milorad Mirilović ◽  
Jevrosima Stevanović ◽  
Uroš Glavinić ◽  
...  
Keyword(s):  
Bluetongue Virus ◽  
Control Measure ◽  
Infected Sheep ◽  
Economic Losses ◽  
Biting Midges ◽  
Domestic Ruminants ◽  
Investigation Period ◽  
Bluetongue Disease ◽  
Culicoides Biting Midges ◽  
Veterinary Institute

Abstract Bluetongue, a vector-born disease caused by the Bluetongue virus (BTV) and transmitted by Culicoides biting midges, is considered to be one of the most important diseases of domestic ruminants. The first outbreak of bluetongue in Serbia was reported in 2001, when BTV serotype 9 was identified in sampled materials. In 2014, outbreak of BTV-4 in Serbia caused considerable economic losses affecting sheep, cattle and goats. During this outbreak, BTV-4 was recorded in 644 outbreaks within 49 municipalities, part of 17 administrative regions. From the total number of sheep kept in areas affected by bluetongue (n=1 748 110), 2 083 cases (0.2%) were proven to be BTV-4 infected. Total of 206 infected cattle and 24 infected goats were reported during this investigation period, which represents 0.06% and 0.03% of the total number of cattle and goats kept in affected areas, respectively. The highest incidence of infected sheep, cattle and goats was recorded on the territory covered by veterinary institute of Nis. Recorded lethality in cattle, sheep and goats was 18.45% (n=38), 48.10% (n=1002) and 54.17% (n=13), respectively. The peak of the outbreak was in September and October when 94.43% of the confirmed positive cases, regardless of the species, was recorded. Monitoring of bluetongue disease in Serbia relies on active surveillance programmes aimed at: (i) identification and tracing of susceptible and potentially infected animals and (ii) detection, distribution and prevalence of insect vectors. Vaccination of sheep is planned to be implemented as a control measure against bluetongue in Serbia.

scholarly journals VP2 Exchange and NS3/NS3a Deletion in African Horse Sickness Virus (AHSV) in Development of Disabled Infectious Single Animal Vaccine Candidates for AHSV

2015 ◽  
Vol 89 (17) ◽  
pp. 8764-8772 ◽  
Author(s):  
Sandra G. P. van de Water ◽  
René G. P. van Gennip ◽  
Christiaan A. Potgieter ◽  
Isabel M. Wright ◽  
Piet A. van Rijn
Keyword(s):  
Mammalian Cells ◽  
Reverse Genetics ◽  
African Horse Sickness ◽  
African Horse Sickness Virus ◽  
Vaccine Platform ◽  
Biting Midges ◽  
Content Type ◽  
Vp2 Protein ◽  
Single Animal

ABSTRACTAfrican horse sickness virus (AHSV) is a virus species in the genusOrbivirusof the familyReoviridae. There are nine serotypes of AHSV showing different levels of cross neutralization. AHSV is transmitted by species ofCulicoidesbiting midges and causes African horse sickness (AHS) in equids, with a mortality rate of up to 95% in naive horses. AHS has become a serious threat for countries outside Africa, since endemicCulicoidesspecies in moderate climates appear to be competent vectors for the related bluetongue virus (BTV). To control AHS, live-attenuated vaccines (LAVs) are used in Africa. We used reverse genetics to generate “synthetic” reassortants of AHSV for all nine serotypes by exchange of genome segment 2 (Seg-2). This segment encodes VP2, which is the serotype-determining protein and the dominant target for neutralizing antibodies. Single Seg-2 AHSV reassortants showed similar cytopathogenic effects in mammalian cells but displayed different growth kinetics. Reverse genetics for AHSV was also used to study Seg-10 expressing NS3/NS3a proteins. We demonstrated that NS3/NS3a proteins are not essential for AHSV replicationin vitro. NS3/NS3a of AHSV is, however, involved in the cytopathogenic effect in mammalian cells and is very important for virus release from cultured insect cells in particular. Similar to the concept of the bluetongue disabled infectious single animal (BT DISA) vaccine platform, an AHS DISA vaccine platform lacking NS3/NS3a expression was developed. Using exchange of genome segment 2 encoding VP2 protein (Seg-2[VP2]), we will be able to develop AHS DISA vaccine candidates for all current AHSV serotypes.IMPORTANCEAfrican horse sickness virus is transmitted by species ofCulicoidesbiting midges and causes African horse sickness in equids, with a mortality rate of up to 95% in naive horses. African horse sickness has become a serious threat for countries outside Africa, since endemicCulicoidesspecies in moderate climates are supposed to be competent vectors. By using reverse genetics, viruses of all nine serotypes were constructed by the exchange of Seg-2 expressing the serotype-determining VP2 protein. Furthermore, we demonstrated that the nonstructural protein NS3/NS3a is not essential for virus replicationin vitro. However, the potential spread of the virus by biting midges is supposed to be blocked, since thein vitrorelease of the virus was strongly reduced due to this deletion. VP2 exchange and NS3/NS3a deletion in African horse sickness virus were combined in the concept of a disabled infectious single animal vaccine for all nine serotypes.

Control of Bulking in an Extended Aeration Sewage Treatment Plant

1972 ◽  
Vol 7 (1) ◽  
pp. 13-20
Author(s):  
D.D.P. Cane ◽  
G.J. Farguhar
Keyword(s):  
Dissolved Oxygen ◽  
Control Measure ◽  
Sewage Treatment ◽  
Sewage Treatment Plant ◽  
Treatment Plant ◽  
Effective Control ◽  
Organic Loading Rate ◽  
Organic Loading ◽  
Mixed Liquor ◽  
Air Supply

Abstract A case of filamentous activated sludge bulking was investigated at an extended aeration plant treating wastes from a highway service centre. The purpose of the study was to find an effective control measure for the bulking and, if possible, to determine the cause of the bulking condition. Experiments were conducted to determine the effects upon bulking of: (a) a controlled copper dosage to the mixed liquor, (b) variations in the organic loading rate, and (c) maintenance of high and low dissolved oxygen concentrations in the mixed liquor. The microorganism responsible for the bulking condition was tentatively identified as Sphaerotilus natans. Extensive growths of these bacteria occurred in the sludge when the mixed liquor dissolved oxygen concentration dropped below 0.5 mg/1. Such dissolved oxygen levels had frequently occurred at this plant due to the use of timed aeration cycles and the use of insufficient air supply during peak loading periods. Variations in organic loading rates were found to have no adverse effect on sludge settleability. When bulking was slight, the condition could be improved by increasing the dissolved oxygen level to 1.5 mg/1, or more. The rate at which the filamentous growths could be eliminated from a highly filamentous sludge by increased aeration was very slow, but could be greatly increased by the simultaneous feeding of copper to the mixed liquor at a dosage rate of 1.0 mg/1, based on the raw sewage flows.

Characterizing the effectiveness of COVID-19 mitigation measures: A data-centric approach (Preprint)

2020 ◽  
Author(s):  
Lukman Olagoke ◽  
Ahmet E. Topcu
Keyword(s):  
Control Measure ◽  
Control Measures ◽  
World Health ◽  
Mitigation Measures ◽  
Effective Control ◽  
The World ◽  
Decision Making Processes ◽  
And Performance ◽  
Health Organization ◽  
The Impact

BACKGROUND COVID-19 represents a serious threat to both national health and economic systems. To curb this pandemic, the World Health Organization (WHO) issued a series of COVID-19 public safety guidelines. Different countries around the world initiated different measures in line with the WHO guidelines to mitigate and investigate the spread of COVID-19 in their territories. OBJECTIVE The aim of this paper is to quantitatively evaluate the effectiveness of these control measures using a data-centric approach. METHODS We begin with a simple text analysis of coronavirus-related articles and show that reports on similar outbreaks in the past strongly proposed similar control measures. This reaffirms the fact that these control measures are in order. Subsequently, we propose a simple performance statistic that quantifies general performance and performance under the different measures that were initiated. A density based clustering of based on performance statistic was carried out to group countries based on performance. RESULTS The performance statistic helps evaluate quantitatively the impact of COVID-19 control measures. Countries tend show variability in performance under different control measures. The performance statistic has negative correlation with cases of death which is a useful characteristics for COVID-19 control measure performance analysis. A web-based time-line visualization that enables comparison of performances and cases across continents and subregions is presented. CONCLUSIONS The performance metric is relevant for the analysis of the impact of COVID-19 control measures. This can help caregivers and policymakers identify effective control measures and reduce cases of death due to COVID-19. The interactive web visualizer provides easily digested and quick feedback to augment decision-making processes in the COVID-19 response measures evaluation. CLINICALTRIAL Not Applicable

scholarly journals Enteric Fever Diagnosis: Current Challenges and Future Directions

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 410
Author(s):  
Durga P. Neupane ◽  
Hari P. Dulal ◽  
Jeongmin Song
Keyword(s):  
Diagnostic Tests ◽  
Enteric Fever ◽  
Asymptomatic Carrier ◽  
Diagnostic Methods ◽  
Effective Control ◽  
Future Directions ◽  
Clinical Presentations ◽  
Global Spread ◽  
Life Threatening ◽  
Pros And Cons

Enteric fever is a life-threatening systemic febrile disease caused by Salmonella enterica serovars Typhi and Paratyphi (S. Typhi and S. Paratyphi). Unfortunately, the burden of the disease remains high primarily due to the global spread of various drug-resistant Salmonella strains despite continuous advancement in the field. An accurate diagnosis is critical for effective control of the disease. However, enteric fever diagnosis based on clinical presentations is challenging due to overlapping symptoms with other febrile illnesses that are also prevalent in endemic areas. Current laboratory tests display suboptimal sensitivity and specificity, and no diagnostic methods are available for identifying asymptomatic carriers. Several research programs have employed systemic approaches to identify more specific biomarkers for early detection and asymptomatic carrier detection. This review discusses the pros and cons of currently available diagnostic tests for enteric fever, the advancement of research toward improved diagnostic tests, and the challenges of discovering new ideal biomarkers and tests.

scholarly journals Transcriptome-based identification and characterization of genes responding to imidacloprid in Myzus persicae

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jianyu Meng ◽  
Xingjiang Chen ◽  
Changyu Zhang
Keyword(s):  
Genetic Basis ◽  
Expression Profiles ◽  
Control Measure ◽  
Effective Control ◽  
Agricultural Pest ◽  
Functional Classification ◽  
Quantitative Real Time Pcr ◽  
Underlying Mechanisms ◽  
Identification And Characterization

Abstract Myzus persicae is a serious and widespread agricultural pest, against which, imidacloprid remains an effective control measure. However, recent reports indicate that this aphid has evolved and developed resistance to imidacloprid. This study aimed to elucidate the underlying mechanisms and genetic basis of this resistance by conducting comparative transcriptomics studies on both imidacloprid-resistant (IR) and imidacloprid-susceptible (IS) M. persicae. The comparative analysis identified 252 differentially expressed genes (DEGs) among the IR and IS M. persicae transcriptomes. These candidate genes included 160 and 92 genes that were down- and up-regulated, respectively, in the imidacloprid-resistant strain. Using functional classification in the GO and KEGG databases, 187 DEGs were assigned to 303 functional subcategories and 100 DEGs were classified into 45 pathway groups. Moreover, several genes were associated with known insecticide targets, cuticle, metabolic processes, and oxidative phosphorylation. Quantitative real-time PCR of 10 DEGs confirmed the trends observed in the RNA sequencing expression profiles. These findings provide a valuable basis for further investigation into the complicated mechanisms of imidacloprid resistance in M. persicae.

Development of Multiwalled Carbon Nanotube-Based Immunobiosensor for the Detection of Bluetongue Virus

2021 ◽  
Vol 21 (6) ◽  
pp. 3513-3523
Author(s):  
Madhu Sudan Guray ◽  
Prasad Minakshi ◽  
Basanti Brar ◽  
Ruma Rani ◽  
Upendra P. Lambe
Keyword(s):  
Carbon Nanotube ◽  
Bluetongue Virus ◽  
Diagnostic Methods ◽  
Multiwalled Carbon Nanotube ◽  
Virus Propagation ◽  
Multiwalled Carbon ◽  
Biting Midges ◽  
Animal Products ◽  
Self Assembled Layer ◽  
The Cost

Bluetongue (BT) disease is a noncontagious disease of domestic and wild ruminants (mainly sheep, cattle, deer) caused by the bluetongue virus (BTV) which is an orbivirus of the Reoviridae family and transmitted by vector Culicoides biting midges. It is a reportable disease of considerable socioeconomic concern and of major importance for the international trade of animals and animal products. Conventional diagnostic methods, such as virus propagation and isolation, immunoassays and also various molecular methods have been developed for the detection of the BTV. Here, we present a novel, rapid and pen-side test for the detection of BTV using multiwalled carbon nanotube (MWCNTs) based immunosensor. Though it is not reported yet. The MWCNTs were prepared, characterized and functionalized with carboxyl group. Viral antibodies were conjugated successfully with functionalized MWCNTs and coated on screen printed carbon electrode (SPCE). These SPCE were evaluated by using electrochemical sensor with an antigen specific to BTV antibodies, resulted in the self-assembled layer of antigen–antibody on the surface of SPCE. The approach described in the present study is a prototype for the development of simple and economic diagnostic tool which will provide the routine screening of BT disease at the door of farmers, thereby increasing the income of farmers by decreasing the cost of diagnosis.

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