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Vaccine2018; 36(25); 3584-3592; doi: 10.1016/j.vaccine.2018.05.044

Diagnostic DIVA tests accompanying the Disabled Infectious Single Animal (DISA) vaccine platform for African horse sickness.

Abstract: African Horse Sickness Virus (AHSV) (Orbivirus genus, Reoviridae family) causes high mortality in naïve domestic horses with enormous economic and socio-emotional impact. There are nine AHSV serotypes showing limited cross neutralization. AHSV is transmitted by competent species of Culicoides biting midges. AHS is a serious threat beyond the African continent as endemic Culicoides species in moderate climates transmit the closely related prototype bluetongue virus. There is a desperate need for safe and efficacious vaccines, while DIVA (Differentiating Infected from Vaccinated) vaccines would accelerate control of AHS. Previously, we have shown that highly virulent AHSV with an in-frame deletion of 77 amino acids (aa) in NS3/NS3a is completely safe, does not cause viremia and shows protective capacity. This deletion mutant is a promising DISA (Disabled Infectious Single Animal) vaccine platform, since exchange of serotype specific virus proteins has been shown for all nine serotypes. Here, we show that a prototype NS3 competitive ELISA is DIVA compliant to AHS DISA vaccine platforms. Epitope mapping of NS3/NS3a shows that more research is needed to evaluate this prototype serological DIVA assay regarding sensitivity and specificity, in particular for AHSVs expressing antigenically different NS3/NS3a proteins. Further, an experimental panAHSV PCR test targeting genome segment 10 is developed that detects reference AHSV strains, whereas AHS DISA vaccine platforms were not detected. This DIVA PCR test completely guarantees genetic DIVA based on in silico and in vitro validation, although test validation regarding diagnostic sensitivity and specificity has not been performed yet. In conclusion, the prototype NS3 cELISA and the PCR test described here enable serological and genetic DIVA accompanying AHS DISA vaccine platforms.
Publication Date: 2018-05-11 PubMed ID: 29759377DOI: 10.1016/j.vaccine.2018.05.044Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research focuses on the development of diagnostic tests that differentiate between infected and vaccinated animals (DIVA) for African Horse Sickness using the Disabled Infectious Single Animal (DISA) vaccine platform.

Understanding African Horse Sickness

  • African Horse Sickness Virus (AHSV) belongs to the Orbivirus genus of the Reoviridae family and this virus can cause high fatalities among unvaccinated domestic horses. This has significant economic consequences and can affect the social and emotional livelihood of people who rely on these animals.
  • The virus is transmitted through biting midges of the Culicoides species. Nine serotypes of the virus exist, which show limited cross neutralization – meaning immunity to one does not necessarily imply immunity to another.
  • Because some Culicoides species found in moderate climates can transmit the closely related bluetongue virus, African Horse Sickness represents a serious threat far beyond Africa.

Necessity of DIVA Vaccines

  • Safe and efficacious vaccines are desperately needed to control African Horse Sickness. DIVA (Differentiating Infected from Vaccinated Animals) vaccines, in particular, could accelerate control of the disease by allowing vaccinated animals to be readily distinguished from infected ones.
  • Scientists have previously demonstrated that a highly virulent form of AHSV, with a deletion of 77 amino acids in NS3/NS3a, is safe, does not cause viremia (the presence of virus in the bloodstream), and offers protective capacity. This deletion mutant represents a promising Disabled Infectious Single Animal (DISA) vaccine platform.

The Diagnostic Tests

  • The researchers developed a prototype NS3 competitive ELISA (cELISA) that is DIVA compliant to African Horse Sickness DISA vaccine platforms, meaning it can differentiate between infected and vaccinated animals.
  • However, sensitivity and specificity of this prototype serological DIVA assay need to be further researched, particularly for AHSVs expressing antigenically different NS3/NS3a proteins.
  • The researchers also developed an experimental panAHSV PCR test targeting genome segment 10, which successfully detected reference AHSV strains but not AHS DISA vaccine platforms. This new PCR test guarantees genetic DIVA based on in silico (computer simulated) and in vitro (in a laboratory environment) validation, although the test’s sensitivity and specificity have not yet been validated.

Conclusion

  • In conclusion, the prototype NS3 cELISA and the new PCR test enable serological and genetic DIVA respectively, in line with AHS DISA vaccine platforms.

Cite This Article

APA
van Rijn PA, Maris-Veldhuis MA, Boonstra J, van Gennip RGP. (2018). Diagnostic DIVA tests accompanying the Disabled Infectious Single Animal (DISA) vaccine platform for African horse sickness. Vaccine, 36(25), 3584-3592. https://doi.org/10.1016/j.vaccine.2018.05.044

Publication

ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 36
Issue: 25
Pages: 3584-3592

Researcher Affiliations

van Rijn, Piet A
  • Department of Virology, Wageningen Bioveterinary Research (WBVR), Lelystad, The Netherlands; Department of Biochemistry, Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa. Electronic address: piet.vanrijn@wur.nl.
Maris-Veldhuis, Mieke A
  • Department of Virology, Wageningen Bioveterinary Research (WBVR), Lelystad, The Netherlands.
Boonstra, Jan
  • Department of Virology, Wageningen Bioveterinary Research (WBVR), Lelystad, The Netherlands.
van Gennip, René G P
  • Department of Virology, Wageningen Bioveterinary Research (WBVR), Lelystad, The Netherlands.

MeSH Terms

  • African Horse Sickness / diagnosis
  • African Horse Sickness / immunology
  • African Horse Sickness / prevention & control
  • African Horse Sickness / virology
  • African Horse Sickness Virus / genetics
  • African Horse Sickness Virus / immunology
  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / blood
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitope Mapping
  • Epitopes / chemistry
  • Epitopes / immunology
  • Gene Expression
  • Horses
  • Polymerase Chain Reaction / methods
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Vaccines, Attenuated
  • Viral Nonstructural Proteins
  • Viral Vaccines / administration & dosage

Citations

This article has been cited 7 times.
  1. Schliewert EC, Hooijberg EH, Goddard A. Experimental infection of horses with African horse sickness virus results in overt disseminated intravascular coagulation. Equine Vet J 2026 Mar;58(2):619-629.
    doi: 10.1002/evj.70134pubmed: 41572601google scholar: lookup
  2. Jiménez-Cabello L, Utrilla-Trigo S, Lorenzo G, Ortego J, Calvo-Pinilla E. Epizootic Hemorrhagic Disease Virus: Current Knowledge and Emerging Perspectives. Microorganisms 2023 May 19;11(5).
  3. van Rijn PA, Maris-Veldhuis MA, van Gennip RGP. 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 May 7;13(5).
    doi: 10.3390/v13050857pubmed: 34067226google scholar: lookup
  4. Utrilla-Trigo S, Jiménez-Cabello L, Alonso-Ravelo R, Calvo-Pinilla E, Marín-López A, Moreno S, Lorenzo G, Benavides J, Gilbert S, Nogales A, Ortego J. Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus. Vaccines (Basel) 2020 Jun 29;8(3).
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  5. van Gennip RGP, Drolet BS, Rozo Lopez P, Roost AJC, Boonstra J, van Rijn PA. Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus. Parasit Vectors 2019 Oct 11;12(1):470.
    doi: 10.1186/s13071-019-3722-2pubmed: 31604476google scholar: lookup
  6. van Weezep E, Kooi EA, van Rijn PA. PCR diagnostics: In silico validation by an automated tool using freely available software programs. J Virol Methods 2019 Aug;270:106-112.
  7. Desselberger U. The 13th International Double-Stranded RNA Virus Symposium, Houffalize, Belgium, 24 to 28 September 2018. J Virol 2019 Feb 15;93(4).
    doi: 10.1128/JVI.01964-18pubmed: 30723139google scholar: lookup