The deletion of the ORF1 and ORF71 genes reduces virulence of the neuropathogenic EHV-1 strain Ab4 without compromising host immunity in horses.
Authors: Wimer Christine L, Schnabel Christiane L, Perkins Gillian, Babasyan Susanna, Freer Heather, Stout Alison E, Rollins Alicia, Osterrieder Nikolaus, Goodman Laura B, Glaser Amy, Wagner Bettina
Journal: PloS one
Summary
# Editorial Summary: ORF1/71 Gene Deletion Reduces EHV-1 Virulence Without Compromising Immune Response Equine herpesvirus type 1 (EHV-1) remains a significant threat to equine health, and the search for effective vaccines continues. Previous in vitro work suggested that the ORF1 and ORF71 genes, which encode immune-evasion proteins, might be targets for attenuating the virus whilst maintaining protective immunity; this study tested that hypothesis in vivo using the neuropathogenic Ab4 strain. Researchers experimentally infected EHV-1-naïve horses with either a double-deletion mutant (Ab4ΔORF1/71), the parent Ab4 strain, or a non-infected control group, then monitored clinical signs, viral shedding, and immune responses over 114 days. Horses infected with Ab4ΔORF1/71 showed markedly reduced clinical disease—notably absent was the characteristic high fever peak seen with wild-type Ab4—and only one of five horses shed virus nasally compared to five of five in the parent strain group, despite both groups developing comparable viremia. Critically, whilst initial antibody and interferon responses were slightly delayed in the deletion mutant group, by day 12 post-infection serum antibody titres were indistinguishable between groups and remained elevated through day 114; furthermore, T-cell immunity (particularly CD8+ IFN-γ responses) developed normally in both cohorts. These findings suggest that Ab4ΔORF1/71 represents a promising vaccine platform, maintaining the immunogenicity needed for protection whilst substantially reducing the clinical and shedding risks associated with natural EHV-1 infection—a particularly valuable prospect
Read the full abstract on PubMed
Practical Takeaways
- •The Ab4ΔORF1/71 mutant shows promise as a safer vaccine candidate—it reduces clinical disease severity (fever, shedding) while maintaining protective immune responses comparable to wild-type virus
- •Gene deletions that reduce virulence without compromising immunity may enable development of live attenuated EHV-1 vaccines with improved safety profiles for field use
- •This approach could reduce transmission risk and clinical complications in vaccinated horses while preserving the broad immune protection of live virus vaccines
Key Findings
- •Ab4ΔORF1/71 deletion mutant showed reduced virulence with no initial fever peak compared to parent Ab4 strain
- •Nasal shedding reduced to 1/5 horses in mutant group versus 5/5 in parent strain group
- •Ab4ΔORF1/71 induced comparable antibody responses (IgG1 and IgG4/7) and cellular immunity (CD8+ IFN-γ+ T-cells) to parent Ab4 strain by day 12 and day 32 post-infection respectively
- •Both virus groups developed similar viremia levels, indicating ORF1/ORF71 genes do not regulate mononuclear cell infection