Equine herpesvirus-1 strain KyA, a candidate vaccine strain, reduces viral titers in mice challenged with a pathogenic strain, RacL

The equine herpesvirus type-1 (EHV-1) strain Kentucky A (KyA) has a long history of repeated passage either in vivo in the Syrian hamster or in vitro in mouse L-M fibroblast tissue culture. This repeated passage in cells other than those of the natural host has caused genomic alterations of the KyA chromosome resulting in deletion of several genes or portions of open reading frames (ORFs). This report presents in vivo data from a mouse model of EHV-1 infection demonstrating the attenuated nature of EHV-1 strain KyA and that intranasal infection with KyA protects animals from subsequent challenge with a pathogenic strain, RacL, by reducing RacL viral titers in the lungs of the challenged animals. Mice infected with KyA exhibit no clinical manifestations of EHV-1 disease and do not experience the wasting that occurs with RacL infection. KyA-infected mice clear virus from the lung by day 5 post-infection (p.i.), whereas RacL infected mice have substantial virus titers (5 × 105 pfu/lung) at this time point. Intranasal infection with KyA followed by a challenge with RacL 4 weeks post-KyA infection results in a significant (P = 0.0079) reduction in the lung titers of the RacL virus. RacL was identified as the virus present in the lungs of the challenged mice by a PCR assay employing primers to amplify the EUS4 gene which differs in size by 1.2 kilobase pairs (kbp) in the two strains. Importantly, the protection afforded by KyA is long lasting in that challenge with RacL 15 months after KyA infection, results in reduced virus titers and viral clearance by day 5 post-challenge. These results support the further consideration of EHV-1 KyA as a live virus vaccine.