Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity

Area of Science:

• Veterinary Virology
• Immunology
• Vaccine Development

Background:

• Equid alphaherpesvirus 1 (EHV-1) causes equine herpesvirus myeloencephalopathy (EHM), significantly impacting the horse racing industry.
• Developing effective EHV-1 vaccines is crucial for preventing infection and managing outbreaks.
• Live attenuated vaccines targeting neuropathogenic and immune evasion genes are a promising strategy.

Purpose of the Study:

• To create and evaluate EHV-1 mutant viruses lacking specific genes (ORF38 and ORF37/38) for their neuropathogenicity and immunogenicity.
• To assess the potential of these mutants as live attenuated vaccines against EHV-1.

Main Methods:

• Construction of EHV-1 mutants: ∆ORF38 and ∆ORF37/38.
• Assessment of neuropathogenicity and viral DNA load in hamster brains after dexamethasone-induced reactivation.
• Evaluation of immunogenicity and protective efficacy against lethal EHV-1 challenge in hamsters following intranasal vaccination.

Main Results:

• The ∆ORF37/38 mutant showed no neuropathogenicity or viral DNA load in brains post-reactivation.
• Intranasal vaccination with ∆ORF37/38 induced a stronger immune response than ∆ORF38.
• Hamsters vaccinated with ∆ORF37/38 were protected against a lethal EHV-1 challenge.

Conclusions:

• Deletion of ORF37/38 in EHV-1 significantly reduces neuropathogenicity and latent infection.
• The ∆ORF37/38 mutant is a promising candidate for a live attenuated EHV-1 vaccine, offering protection and reduced disease risk.