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Veterinary research2026; doi: 10.1186/s13567-026-01753-7

Multivalent Disabled Infectious Single Animal (DISA)-DIVA vaccine for all nine serotypes of African horse sickness virus (AHSV) is broadly protective in IFNAR (-/-) mice.

Abstract: African horse sickness (AHS) is a highly severe, midge-borne disease of equids showing a mortality rate of > 90% in naive domestic horses. Outbreaks are caused by AHS virus (AHSV) and result in devastating economic losses in developing countries as equids play a crucial role in the agricultural industry and many households. The AHSV species encompasses nine serotypes showing no or limited cross protection, which is challenging regarding AHS vaccine development. Recently, and like bluetongue virus (BTV), the AHS Disabled Infectious Single Animal (DISA)-DIVA vaccine platform was developed and applied for all nine AHSV serotypes. The vaccine platform is based on a single deletion crucial for vaccine safety and affording differentiation of infected from vaccinated individuals (DIVA) testing. Before considering ethically debatable and expensive experiments in equids, DISA-DIVA vaccine candidates were evaluated here in the previously validated IFNAR (-/-) mouse model for AHS. A multivalent AHS DISA-DIVA vaccine containing DISA constructs for each of the nine serotypes was studied. This "DISA cocktail" was safe and protected mice against two virulent AHSV serotypes used in challenge infection studies. DISA multivalent vaccine induced serotype-specific neutralizing antibodies (nAbs) against all AHSV serotypes suggesting broad protection, as correlates of protection (CoP) based on nAb titers for studied serotypes can be extrapolated to others. These results now justify further experiments in horses to study safety, efficacy and DIVA by DISA cocktail vaccine. Importantly, the presented results for IFNAR (-/-) mice indicate that broad protection of equines by vaccination with DISA cocktail vaccine can be feasible.
© 2026. The Author(s).
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Publication Date: 2026-04-16 PubMed ID: 41987248DOI: 10.1186/s13567-026-01753-7Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study developed and tested a multivalent vaccine targeting all nine serotypes of African horse sickness virus (AHSV) in a mouse model, showing broad protection and safety, with the goal to advance to trials in horses.

Background on African Horse Sickness (AHS) and AHSV

  • African horse sickness is a deadly disease affecting horses, transmitted by biting midges, with mortality rates over 90% in horses that have no prior immunity.
  • The disease causes major economic losses, especially in developing countries where horses and related equids are vital to agriculture and household livelihoods.
  • AHS is caused by African horse sickness virus (AHSV), which has nine distinct serotypes that provide little to no cross-protection against each other.
  • The diversity of serotypes makes vaccine development challenging as protection needs to cover all variants.

DISA-DIVA Vaccine Platform

  • The Disabled Infectious Single Animal (DISA)-DIVA platform is a novel vaccine technology recently applied to viruses similar to AHSV, like bluetongue virus.
  • This vaccine platform involves deletion of a critical viral gene, making virus replication defective and ensuring vaccine safety.
  • The deletion also allows for DIVA (Differentiating Infected from Vaccinated Animals) testing, enabling distinction between vaccinated and naturally infected animals, an important feature for disease surveillance and control.
  • This platform has been developed for all nine AHSV serotypes individually.

Study Design and Models

  • Ethical concerns and cost limit initial testing in horses (natural host), so the researchers used an established IFNAR knockout (IFNAR -/-) mouse model susceptible to AHSV infection.
  • A multivalent vaccine “cocktail” was created by combining the DISA-DIVA constructs from all nine serotypes into one vaccine formulation.
  • Mice were vaccinated with this multivalent vaccine and later challenged with two virulent AHSV serotypes to evaluate safety and protection.

Key Findings

  • The multivalent DISA-DIVA vaccine cocktail was found to be safe in the IFNAR -/- mouse model, showing no adverse effects.
  • Vaccinated mice were protected against challenge infections with two virulent AHSV serotypes, demonstrating protective efficacy.
  • Serological tests showed the vaccine induced serotype-specific neutralizing antibodies (nAbs) against all nine serotypes, indicating broad immune coverage.
  • The presence of neutralizing antibodies is linked to protection (correlate of protection), thus nAb titers from tested serotypes suggest the vaccine will protect against others as well.

Implications and Next Steps

  • The success in mouse models supports moving forward with trials in horses, to assess vaccine safety, efficacy, and ability to distinguish vaccinated from infected animals (DIVA) in the natural host.
  • Developing a broadly protective vaccine for all AHSV serotypes could drastically reduce disease impact and economic losses in affected regions.
  • The study provides evidence that a multivalent vaccine approach using the DISA-DIVA platform is feasible for controlling African horse sickness.

Cite This Article

APA
Utrilla-Trigo S, Jiménez-Cabello L, van Gennip RGP, van Rijn PA, Ortego J, Calvo-Pinilla E. (2026). Multivalent Disabled Infectious Single Animal (DISA)-DIVA vaccine for all nine serotypes of African horse sickness virus (AHSV) is broadly protective in IFNAR (-/-) mice. Vet Res. https://doi.org/10.1186/s13567-026-01753-7

Publication

Veterinary research
ISSN: 1297-9716
NlmUniqueID: 9309551
Country: England
Language: English

Researcher Affiliations

Utrilla-Trigo, Sergio
  • Centro de Investigación en Sanidad Animal, CISA-CSIC, Valdeolmos, Madrid, Spain.
Jiménez-Cabello, Luis
  • Centro de Investigación en Sanidad Animal, CISA-CSIC, Valdeolmos, Madrid, Spain.
van Gennip, René G P
  • Wageningen Bioveterinary Research (WBVR), Lelystad, The Netherlands.
van Rijn, Piet A
  • Wageningen Bioveterinary Research (WBVR), Lelystad, The Netherlands.
  • Department of Biochemistry, Centre for Human Metabolomics, North-West University, Potchefstroom, South Africa.
Ortego, Javier
  • Centro de Investigación en Sanidad Animal, CISA-CSIC, Valdeolmos, Madrid, Spain. ortego@inia.csic.es.
Calvo-Pinilla, Eva
  • Centro de Investigación en Sanidad Animal, CISA-CSIC, Valdeolmos, Madrid, Spain. calvo.eva@inia.csic.es.

Conflict of Interest Statement

Declarations. Ethics approval and consent to participate: Animal experimental protocols were approved by the Ethical Review Committee at the INIA-CISA and Comunidad de Madrid (Permit number: PROEX 075.2/22) in strict accordance with EU guidelines 2010/63/UE about protection of animals used for experimentation, and other scientific purposes and Spanish Animal Welfare Act 32/2007. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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