Development of African horse sickness disabled infectious single animal (DISA)-DIVA vaccine platform applied for all nine serotypes.

Overview

• This research focuses on developing a novel vaccine platform called DISA-DIVA for African horse sickness (AHS), targeting all nine virus serotypes.
• The vaccine is designed to be safer than existing vaccines and allows differentiation between vaccinated and naturally infected horses.

Background

• African Horse Sickness (AHS) is a severe viral disease affecting horses and related equids, with a mortality rate of up to 95% in naive domestic horses.
• The causative agent, African horse sickness virus (AHSV), belongs to the genus Orbivirus, family Sedoreoviridae, and has nine distinct serotypes with limited cross-protection.
• AHSV is transmitted by Culicoides biting midges, making the disease a major concern in Africa and a threat to other regions with competent vectors.
• Outbreaks cause significant economic losses, especially in developing African countries and the equestrian industry worldwide.

Current Vaccine Challenges

• Existing live-attenuated vaccines (LAVs) for AHS have safety concerns; they may still cause disease.
• It is difficult to distinguish infected animals from vaccinated ones using current tests, complicating outbreak control and surveillance.
• Vector-borne transmission risks and risks associated with vaccine virus spread are problems with current vaccine approaches.

New Vaccine Platform: DISA-DIVA

• DISA-DIVA stands for Disabled Infectious Single Animal – Differentiating Infected from Vaccinated Animals.
• The vaccine platform involves a deliberate deletion in genome segment 10 of AHSV, which eliminates virulence and disables replication beyond a single infected animal.
• This modification ensures the vaccine virus cannot spread via midges or between animals, increasing safety significantly.
• The “DIVA” capability means vaccinated horses can be differentiated from naturally infected horses using a specific PCR test targeting the deleted genome segment, aiding in surveillance and control.

Application to All Nine Serotypes

• The researchers developed nine different vaccine candidates, named DISA1 through DISA9, corresponding to each of the nine AHSV serotypes.
• They exchanged genome segments 2 and 6 in the vaccine virus, which encode the outer shell proteins responsible for serotype-specific immune responses.
• This approach allows each vaccine to induce immunity specifically tailored to one AHSV serotype.

Validation and Testing

• The nine DISA vaccines were extensively tested in vitro to confirm their safety and suitability.
• The accompanying DIVA PCR test was developed and validated to detect the unique deletion in the vaccine viruses.
• Based on previous research, these vaccines are:
• Non-virulent (do not cause disease).
• Non-transmissible by the Culicoides midges (do not spread between animals).
• Distinguishable from wildtype (natural) AHSV using the DIVA test.

Next Steps

• The DISA vaccines are now ready for vaccination-challenge experiments in horses, the target host species.
• These experiments will assess the vaccines’ efficacy, safety, and ability to elicit protective immunity.
• Successful development could provide a safer, more effective AHS vaccine platform suitable for all serotypes and improve disease control globally.