Equine disease model for herpesvirus neurologic disease and uses thereof

Abstract

The present invention relates to an in vivo equine disease model for equine herpesvirus-1 neurological disease comprising a horse having a low pre-exposure level of herpesvirus-specific CTL precursors and/or is approximately 20 years of age or older wherein the horse is experimentally infected with a neuropathogenic strain of equine herpesvirus or a mutant thereof. The invention includes a method of preparing an in vivo equine disease model for equine herpesvirus-1 neurological disease comprising obtaining a horse that possesses low pre-infection levels of EHV-1 specific CTL precursors and/or is approximately 20 years of age or older and inoculating the horse intranasally with an effective infecting amount of a neuropathogenic strain of EHV-1. A particularly preferred method involves the advanced neurological disease stage when the experimental horse presents clinical signs of myeloencephalopathy. Additionally, the invention concerns a method of quantifying the risk factors and predicting the development of clinical neurologic signs of equine herpesvirus-1 neurological disease in a horse comprising the steps of (a) determining the pre-infection CTLp frequency to be less than approximately 40 EHV-1 specific CTLp per 10 6 PBMC; and (b) determining the post-infection viremic load following exposure to EHV-1 to be approximately 10-fold or more over the viremic load present in horses following exposure to a non-neuropathogenic strain of EHV-1. Also described in the invention is the determination of the risk of developing the clinical neurologic signs by use of an equation y=a+bx wherein y is the peak viremic load, a=2.97, b=−0.027 and the variable x is the pre-infection CTLp frequency. Lastly, the invention deals with a new live, attenuated vaccine formulation that is effective against neurologic disease due to equine herpesvirus-1.

What is claimed is: 
     
         1 . A method of protecting a horse against neurologic disease or viral infection caused by a neuropathogenic strain of EHV-1 comprising administering to the horse in need of protection an immunologically effective amount of an equine vaccine which comprises a nontoxic, physiologically acceptable carrier and an immunogenic amount of a non-neuropathogenic strain of EHV-1 having an ORF30 A 2254  genotype. 
     
     
         2 . The method according to  claim 1 , wherein the non-neuropathogenic strain of EHV-1 is live and attenuated. 
     
     
         3 . The method according to  claim 1 , wherein the non-neuropathogenic strain of EHV-1 is T262. 
     
     
         4 . The method according to  claim 1 , comprising administering the equine vaccine which further comprises an antigen selected from the group consisting of: EHV-4, EHV-5, Equine Influenza Virus, Eastern Encephalomyelitis Virus, Western Encephalomyelitis Virus, Venezuelan Encephalomyelitis Virus, West Nile Virus, African Horse Sickness Virus, tetanus toxoid,  Streptococcus equi, Rhodococcus equi,  leptospira,  Clostridum difficile, Sarcocystis neurona, Neospora hughesi,  a recombinant protein or a recombinant vector expressing a protein derived therefrom and a combination thereof. 
     
     
         5 . The method according to  claim 1 , which comprises administering the vaccine orally, intranasally, intramuscularly, intrarectally, transdermally or intradermally to the horse. 
     
     
         6 . The method according to  claim 1 , further comprising administering an adjuvant immediately before, during or after the equine vaccine is administered. 
     
     
         7 . The method according to  claim 6 , wherein the adjuvant comprises squalane and a polyoxypropylene-polyoxyethylene block copolymer. 
     
     
         8 . The method according to  claim 1 , comprising administering the equine vaccine which further comprises an adjuvant. 
     
     
         9 . The method according to  claim 8 , wherein the adjuvant comprises squalane and a polyoxypropylene-polyoxyethylene block copolymer. 
     
     
         10 . The method according to  claim 4 , which comprises administering the vaccine orally, intranasally, intramuscularly, intrarectally, transdermally or intradermally to the horse. 
     
     
         11 . The method according to  claim 4 , further comprising administering an adjuvant immediately before, during or after the equine vaccine is administered. 
     
     
         12 . The method according to  claim 11 , wherein the adjuvant comprises squalane and a polyoxypropylene-polyoxyethylene block copolymer. 
     
     
         13 . The method according to  claim 4 , comprising administering the equine vaccine which further comprises an adjuvant. 
     
     
         14 . The method according to  claim 13 , wherein the adjuvant comprises squalane and a polyoxypropylene-polyoxyethylene block copolymer.