The equine immune response to viral respiratory disease.

摘要

The aim of the research described in this thesis was to study the equine immune response to viral respiratory disease. In the horse, equine influenza virus and equine herpesvirus-1 (EHV-1) are the most common causes of viral respiratory disease. A study of the immune responses to these agents was appealing because these viruses are quite different in terms of the type of immune response that they generate. For protection from equine influenza virus, serum and mucosal antibody responses are critical. In contrast, protection from EHV-1 is dependent on cytotoxic T-lymphocyte (CTL) responses. The work on equine influenza virus examined the efficacy of particle-mediated DNA vaccination with the equine influenza virus hemagglutinin (HA) gene. In addition, the regulation and distribution of immune responses following influenza virus infection and DNA vaccination were studied extensively. The goal of the EHV-1 studies was to identify viral proteins that induce protective CTL responses. As a secondary goal we tested the efficacy of particle mediated DNA vaccination as a potential vaccination strategy for protection from EHV-1.; Common features of immune responses to both influenza virus infection and HA DNA vaccination were virus-specific IgGa, and IgGb antibody responses, and IFN-γ mRNA responses, which were associated with protection from infection. However, these immune responses differed markedly in their regional distribution in the body, and there was no mucosal IgA response to DNA vaccination.; Our studies of EHV-1 used an in vitro assay for detection of EHV-1 proteins containing CTL epitopes. Using this assay we showed that the immediate early protein induced CTLs in ponies expressing a specific MHC I haplotype (designated ELA-A3.1 in the horse). In contrast to our influenza virus studies, particle mediated DNA vaccination of ponies with different EHV-1 genes was ineffective for inducing protection, as this strategy could not elicit CTL responses. In the future, the in vitro technique developed here can be used to study the immunogenicity of EHV-1 proteins in horses with a range of MHC I genes. This information could them be used in conjunction with vaccination strategies capable of eliciting CTL responses with the long-term goal of developing an effective EHV-1 vaccine.