Abstract
The equine herpesvirus type 1 (EHV-1) ORF1 and ORF71 genes have immune modulatory effects in vitro. Experimental infection of horses using virus mutants with multiple deletions including ORF1 and ORF71 showed promise as vaccine candidates against EHV-1. Here, the combined effects of ORF1 and ORF71 deletions from the neuropathogenic EHV-1 strain Ab4 on clinical disease and host immune response were further explored. Three groups of EHV-1 naïve horses were experimentally infected with the ORF1/71 gene deletion mutant (Ab4ΔORF1/71), the parent Ab4 strain, or remained uninfected. In comparison to Ab4, horses infected with Ab4ΔORF1/71 did not show the initial high fever peak characteristic of EHV-1 infection. Ab4ΔORF1/71 infection had reduced nasal shedding (1/5 vs. 5/5) and, simultaneously, decreased intranasal interferon (IFN)-α, interleukin (IL)-10 and soluble CD14 secretion. However, Ab4 and Ab4ΔORF1/71 infection resulted in comparable viremia, suggesting these genes do not regulate the infection of the mononuclear cells and subsequent viremia. Intranasal and serum anti-EHV-1 antibodies to Ab4ΔORF1/71 developed slightly slower than those to Ab4. However, beyond day 12 post infection (d12pi) serum antibodies in both virus-infected groups were similar and remained increased until the end of the study (d114pi). EHV-1 immunoglobulin (Ig) G isotype responses were dominated by short-lasting IgG1 and long-lasting IgG4/7 antibodies. The IgG4/7 response closely resembled the total EHV-1 specific antibody response. Ex vivo re-stimulation of PBMC with Ab4 resulted in IFN-γ and IL-10 secretion by cells from both infected groups within two weeks pi. Flow cytometric analysis showed that IFN-γ producing EHV-1-specific T-cells were mainly CD8+/IFN-γ+ and detectable from d32pi on. Peripheral blood IFN-γ+ T-cell percentages were similar in both infected groups, albeit at low frequency (~0.1%). In summary, the Ab4ΔORF1/71 gene deletion mutant is less virulent but induced antibody responses and cellular immunity similar to the parent Ab4 strain.
Highlights
Equine herpesvirus type-1 (EHV-1) is highly prevalent in the equine population with most horses becoming infected as juveniles and remaining latently infected for life [1]
The results demonstrate that Ab4ΔORF1/71 is an interesting vaccine candidate because of its ability to induce antibody responses and cellular immunity similar to the parent Ab4 strain while being less virulent
Further evaluation of Ab4ΔORF1/71 in a challenge and protection study is needed to determine its full potential as a vaccine candidate, especially in respect to preventing cell-associated viremia after EHV-1 challenge
Summary
Equine herpesvirus type-1 (EHV-1) is highly prevalent in the equine population with most horses becoming infected as juveniles and remaining latently infected for life [1]. Infected horses act as a virus reservoir. EHV-1 spreads through respiratory secretions and nose-to-nose contact or via fomites. EHV-1 first infects the respiratory epithelium, causing fever and rhinopneumonitis. Disease manifestations range from subclinical to severe respiratory infection, abortion, neonatal foal death, or equine herpesvirus myeloencephalopathy (EHM) [1,4]. Arteriolar vasculitis and subsequent thrombosis and ischemia causes both the abortigenic and neurologic manifestations [1, 5, 6]. In the past 20 years, the increased incidence of morbidity and mortality due to the neurologic manifestation has prompted heightened biosecurity and resurgence in EHV-1 vaccine research [4, 10, 11]
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