African horse sickness virus (AHSV) with a deletion of 77 amino acids in NS3/NS3a protein is not virulent and a safe promising AHS Disabled Infectious Single Animal (DISA) vaccine platform.

The research article discusses the development of a safe vaccine for African horse sickness virus (AHSV) that has proven efficacy in initial trials. The vaccine works through the deletion of 77 amino acids in the NS3/NS3a protein of the virus, resulting in a non-virulent strain.

About African horse sickness virus (AHSV)

• AHSV is a virus species that belongs to the Orbivirus genus within the family of Reoviridae. Nine distinct serotypes of this virus have been identified, each displaying limited cross neutralization.
• Transmission occurs via species of Culicoides biting midges, and it causes African Horse Sickness (AHS) in equids, particularly horses. The disease can be deadly, with mortality rates reaching up to 95% amongst naïve domestic horses who have had no prior exposure.
• Beyond Africa, AHS poses a significant threat as indigenous Culicoides species in moderate climates can effectively transmit related viruses, such as the bluetongue virus.
• AHS takes a huge economic toll in affected developing countries. In developed nations, it could lead to financial hardships in the equestrian industry and serve as a cause for emotional distress for horse owners.

Current AHS vaccines and their limitations

• Live-attenuated vaccine viruses (LAVs) for AHS have been developed but their safety has been questioned due to potential risks like residual virulence, reversion to virulence, and the emergence of virulent variants through reassortment with existent AHSV strains in the field.
• Thus, there is active research aiming to develop vaccines with improved safety and efficacy profiles.

Developing the AHS Disabled Infectious Single Animal (DISA) vaccine

• Reverse genetics has recently been employed for AHSV research, providing new avenues for vaccine development. This includes the development of the Disabled Infectious Single Animal (DISA) vaccine for AHS.
• In this study, a virulent AHSV5 strain was isolated and its virulence was confirmed through experimental infection of ponies.
• ‘Synthetically derived’ AHSV5 strain with an in-frame deletion of 77 amino acid codons in genome segment 10 (which encodes the NS3/NS3a protein) was created. This deletion resulted in in vitro characteristics similar to those of previously studied NS3/NS3a knockout mutants of LAV strain AHSV4LP.
• Unlike its virulent ancestor, the deletion AHSV5 mutant (DISA5) proved to be safe for ponies. Moreover, two rounds of vaccination with DISA5 or with a DISA vaccine based on LAV strain AHSV4LP proved to be protective against lethal AHSV exposure.
• However, to improve upon these initial findings, this research suggests the need for further exploration of the AHS DISA vaccine platform for all nine AHSV serotypes, the vaccine’s efficacy and to gain a more detailed understanding of the vaccine’s profile.