Identifier

etd-11162015-102110

Degree

Doctor of Philosophy (PhD)

Department

Veterinary Medical Sciences - Pathobiological Sciences

Document Type

Dissertation

Abstract

Equine Herpesvirus 1 (EHV-1) is an important ubiquitous enzootic equine pathogen and one of the most common pathogens of the horse, causing, respiratory disease, epidemic abortion, occasionally neurological disease in horses, which leads to significant economic losses to the horse industry. EHV-1 induces several clinical signs of disease ranging in severity, from mild respiratory disease to abortion in pregnant mares, neonatal foal death and neuropathogenic disorders. Natural EHV-1 infection stimulated short lived protective immunity and had both humoral and cellular immune responses. Currently vaccination remains the best option to prevent EHV-1 infection and different applications of vaccination have been investigated and developed over the past decades. The objective of this research was the design of a safe and effective virus-vectored vaccine to prevent EHV-1 infections. In this research, EHV-1 glycoprotein D (gD) gene was cloned into the Herpes Simplex Virus Type-1 (HSV-1) VC2 vector, which contains the gK∆31-68 deletion and UL20∆2-22 deletion. The VC2 strain cannot infect axonal neurons of mice and rats and has been shown to produce protective immune responses against both HSV-1 and HSV-2 viruses in mice and guinea pigs. Vaccination of mice with the HSV-VC2-EHV-gD increased virus neutralizing activities against EHV-1 (33.6%) in mice after three vaccinations, which was similar to commercial whole virus vaccine group (32.6%) and significantly higher than VC2 and Unvaccinated control groups (p<0.01 or p<0.001). Mice vaccinated with the VC2-EHV-gD group exhibited significantly higher humoral and cellular immune responses as detected by polychromatic flow cytometry when compared to the other groups (p<0.01 or p<0.001). Induction of IgG1 and IgG2a antibodies were significantly higher in the VC2-EHV-gD group than other groups after three vaccinations (p<0.001). It’s interesting that induction of IgM antibody in the Vetera group was significantly higher than other groups before and after challenge (p<0.01 or P<0.05). Vaccination with the VC2-EHV-gD also stimulated strong cellular immune response (IFN-γ and TNF). Additional studies are needed to assess the VC2-EHV-gD vaccine efficacy in generating protective humoral and cellular immune responses in horses.

Date

2015

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Kousoulas, Konstantin G.

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