Antibody and cellular immune responses following DNA vaccination and EHV-1 infection of ponies
Department of Clinical Sciences, College of Veterinary Medicine, Colorado State University, 300W. Drake Rd., Fort Collins, Colorado 80523, USA. Veterinary Immunology and Immunopathology
(Impact Factor: 1.54).
06/2006; 111(1-2):81-95. DOI: 10.1016/j.vetimm.2006.01.011
Equine herpesvirus-1 (EHV-1) is the cause of serious disease with high economic impact on the horse industry, as outbreaks of EHV-1 disease occur every year despite the frequent use of vaccines. Cytotoxic T-lymphocytes (CTLs) are important for protection from primary and reactivating latent EHV-1 infection. DNA vaccination is a powerful technique for stimulating CTLs, and the aim of this study was to assess antibody and cellular immune responses and protection resulting from DNA vaccination of ponies with combinations of EHV-1 genes. Fifteen ponies were divided into three groups of five ponies each. Two vaccination groups were DNA vaccinated on four different occasions with combinations of plasmids encoding the gB, gC, and gD glycoproteins or plasmids encoding the immediate early (IE) and early proteins (UL5) of EHV-1, using the PowderJect XR research device. Total dose of DNA/plasmid/vaccination were 25 microg. A third group comprised unvaccinated control ponies. All ponies were challenge infected with EHV-1 6 weeks after the last vaccination, and protection from clinical disease, viral shedding, and viremia was determined. Virus neutralizing antibodies and isotype specific antibody responses against whole EHV-1 did not increase in either vaccination group in response to vaccination. However, glycoprotein gene vaccinated ponies showed gD and gC specific antibody responses. Vaccination did not affect EHV-1 specific lymphoproliferative or CTL responses. Following challenge infection with EHV-1, ponies in all three groups showed clinical signs of disease. EHV-1 specific CTLs, proliferative responses, and antibody responses increased significantly in all three groups following challenge infection. In summary, particle-mediated EHV-1 DNA vaccination induced limited immune responses and protection. Future vaccination strategies must focus on generating stronger CTL responses.
Available from: Magda Dunowska
- "As with other viral infections, both humoral and cell-mediated immune responses are generated by infected or vaccinated horses (Soboll et al. 2006; Paillot et al. 2007). The duration of immunity following EHV-1 infection is thought to be short, and re-infection can occur every 3–6 months (Bryans 1969, 1980). "
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ABSTRACT: Abstract Equid herpesvirus (EHV) type 1 is a common pathogen of horses with worldwide distribution. Although severe tracheobronchitis has been described in some field outbreaks of EHV-1 respiratory disease, many EHV-1 infections occur asymptomatically or are accompanied only by signs of mild respiratory disease. However, EHV-1 infection can also result in outcomes other than respiratory disease such as abortion, neonatal death or neurological disease. This review provides an overview of the diagnosis, treatment and prognosis for EHV-1 associated diseases, with an emphasis on neurological presentations of EHV-1 infection. Pathogenesis and epidemiology of EHV-1 associated diseases are described in an accompanying paper (Dunowska 2014).
Available from: Carine L Holz
- "Serum neutralization (SN) titers for experiments 2 and 3 were determined on days -1, 7, 14 and 21 pi as previously described . "
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ABSTRACT: Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group.
- "The efficacy of DNA vaccines has also been evaluated. A combination of plasmids expressing gB, gC, and gD or plasmids expressing the IE protein (ICP4) and the early UL5 gene product were used to immunize ponies and were shown to induce only limited immune responses and protection against EHV-1 challenge (Soboll et al., 2006). "
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ABSTRACT: The equine herpesviruses type 1 (EHV-1) and 4 (EHV-4) are ubiquitous pathogens that affect horse populations on all continents. Despite widespread vaccination, EHV-1 and EHV-4 infections remain a permanent risk. While the two viruses share a high degree of genetic and antigenic similarity, they differ significantly in host range and pathogenicity. Compared to EHV-4, which mainly infects horses and causes respiratory disease, EHV-1 has a broader host range and can result in respiratory disease, abortions, neonatal death, and equine herpesvirusmyeloencephalopathy (EHM). Recent studies have elucidated a number of mechanisms that may, at least partly, explain the differential pathogenic potential of the two viruses. While both EHV-1 and EHV-4 can escape host immune responses and establish latent infection, there are differences with respect to virus entry and their ability to interfere with the innate immune response. Understanding the virus' repertoire of immunomodulatory mechanisms may lead the way to develop more efficient vaccines.
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