Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity.
Authors: Schnabel Christiane L, Wimer Christine L, Perkins Gillian, Babasyan Susanna, Freer Heather, Watts Christina, Rollins Alicia, Osterrieder Nikolaus, Wagner Bettina
Journal: BMC veterinary research
Summary
# Editorial Summary: ORF2 Gene Deletion in EHV-1 as a Potential Vaccine Strategy Equine herpesvirus type 1 (EHV-1) remains a significant threat to equine health, causing respiratory disease, abortion, and the particularly concerning neuropathogenic form of infection; identifying and characterising the viral genes responsible for disease severity is therefore crucial for developing safer immunological interventions. Schnabel and colleagues experimentally infected 24 Icelandic horses (aged 2–4 years) with either virulent EHV-1 Ab4 or a genetically modified variant lacking the ORF2 gene (Ab4ΔORF2), monitoring clinical signs, viral shedding, viraemia, and both humoral and cell-mediated immune responses over 260 days. The ORF2-deleted mutant produced markedly reduced clinical disease and lower peak viraemia compared to wild-type infection, whilst generating robust antibody responses and CD8+ T-cell immunity comparable to the fully virulent strain. These findings suggest that ORF2 functions as a virulence determinant—likely through immune evasion mechanisms—making the Ab4ΔORF2 construct a promising candidate for a live attenuated vaccine that could confer protective immunity without the clinical complications of natural infection. For practitioners involved in EHV-1 management, this research indicates that future vaccine development may move towards live modified-virus platforms capable of inducing stronger cellular responses than inactivated vaccines, potentially offering superior protection against respiratory and neurological disease.
Read the full abstract on PubMed
Practical Takeaways
- •ORF2 is a key virulence factor in neuropathogenic EHV-1 strains; understanding its role may guide vaccine development strategies
- •Attenuated EHV-1 vaccines lacking ORF2 could potentially provide protection without causing disease, though field efficacy requires further evaluation
- •This research supports rational design of safer EHV-1 vaccines by identifying and removing specific pathogenic genes
Key Findings
- •ORF2 gene deletion in neuropathogenic EHV-1 strain Ab4 reduced virulence compared to wild-type Ab4 strain
- •Ab4ΔORF2 deletion mutant maintained strong immunogenicity despite reduced virulence
- •Clinical presentation, virus shedding, and viremia were monitored over 260 days post-infection in 24 horses across three groups