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
Source: PubMed


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.

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    • "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).
    New Zealand veterinary journal 03/2014; 62(4). DOI:10.1080/00480169.2014.899945 · 1.26 Impact Factor
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    • "Serum neutralization (SN) titers for experiments 2 and 3 were determined on days -1, 7, 14 and 21 pi as previously described [23]. "
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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.
    Veterinary Research 12/2013; 44(1):118. DOI:10.1186/1297-9716-44-118 · 2.82 Impact Factor
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    • "Serum neutralization (SN) titers for both experiments were determined throughout pregnancy and on days–1, 7, 14 and 21 post challenge infection as previously described using Ab4 as a reference strain [23] "
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    ABSTRACT: Equine herpesvirus-1 (EHV-1) continues to cause both sporadic and epidemic abortions despite extensive vaccination. Lack of progress in the development of protective vaccines may be hindered by the lack of equine abortion models that employ contemporary EHV-1 strains. The objective of our experiments was to compare a contemporary EHV-1 strain with a previously described challenge strain, and to quantify EHV-1 loads in various maternal and fetal tissues. Infection experiments were performed in two groups of 7 pregnant pony mares at 270-290 days of gestation with a contemporary EHV-1 strain (University of Findlay 2003 isolate - OH03) or an EHV-1 strain isolated over 30 years ago, and previously described in abortion models (Ab4). All mares in both groups exhibited nasal viral shedding and viremia. Infection with OH03 resulted in 1/7 abortion and infection with Ab4 resulted in 5/7 abortions. In the OH03 challenge, placentas of foals delivered at term showed little detectable virus, while the aborted fetus expressed high levels of virus infection in the spleen and liver, lower levels in the lung and thymus, and lowest levels in the chorioallantois. After Ab4 challenge, high viral loads were detected in fetal and placental tissues in abortions. In the two normal deliveries, the chorioallantois contained virus levels comparable with the chorioallantois of aborted foals and both foals shed EHV-1 starting on day 4 of life, but were clinically healthy. Our results demonstrate the continued importance of strain selection for abortion models, and this study is the first report of viral load quantification using contemporary methods. Extremely high EHV-1 loads in decidua from abortions illustrate the infection risk posed to other horses.
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