Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1)

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Vaccine (Impact Factor: 3.62). 05/2006; 24(17):3636-45. DOI: 10.1016/j.vaccine.2006.01.062
Source: PubMed


Equine herpesvirus type 1 (EHV-1) is a ubiquitous alphaherpesvirus of horses which causes rhinopneumonitis, abortion and myeloencephalopathy. To test the efficacy of commercial vaccines in protection against neurological EHV-1 challenge, groups of five horses were immunized with modified-live virus or an inactivated vaccine, or received placebo. Horses were challenged by aerosol with a recent virus isolate obtained from a case of paralytic EHV-1. The duration of fever decreased significantly in the modified-live virus vaccine group. Three animals in each of the inactivate and control groups showed alterations in neurological status. When compared to the inactivated vaccine, the modified-live virus vaccine induced significantly lower virus-neutralizing antibodies over the course of the study. The modified-live virus vaccine resulted in low EHV-1-specific IgG(T)/IgGa and IgG(T)/IgGb ratios, suggesting a bias towards a cytotoxic immune response. Virus shedding from the nasopharynx was almost undetectable in the modified-live virus group, and was significantly lower when compared to that in the other groups. Normalized lymphocyte viral genome copies were similar for the three groups, although animals vaccinated with the modified-live virus vaccine were qPCR-positive on fewer days when compared to those of the other groups. Based on data from neurological signs, rectal temperatures, virus isolation from nasal swabs and immune response specificity, we concluded that protection induced by the modified-live virus vaccine is superior to that induced by the inactivated combination vaccine.

22 Reads
    • "The MLV vaccine reduced virus shedding after challenge to almost undetectable levels. It also prevented neurological signs but only slightly reduced viremia (Goodman et al., 2006). In another study, the efficacy of the MLV vaccine was compared to an inactivated vaccine with high antigen content for abortion control (Pneumabort K, Pfizer) in an optimized 3-dose vaccination regimen. "
    [Show abstract] [Hide abstract]
    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.
    Veterinary Microbiology 07/2013; 167(1). DOI:10.1016/j.vetmic.2013.06.018 · 2.51 Impact Factor
  • Source
    • "For IgG(T), it was notable that there was a pre-existing titer in all experimental groups despite the fact that SN titers were negligible at this time point, suggesting that IgG(T) responses do not contribute substantially to SN titers or to protective humoral immunity to EHV-1. As it has previously been hypothesized that the IgGb/IgG(T) ratio may predict protection from EHV-1 infection [17], IgGb/IgG(T) ratios were determined in our study, but were negligible, most likely due to the low IgG(T) titers, and hence, may not be of much value for assessing immune responses (data not shown). "
    [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT: Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EHV-1 (WT). Infection with either virus led to cytokine responses that coincided with the course of clinical disease, particularly the biphasic pyrexia, which correlates with respiratory disease and viremia, respectively. Similarly, both viruses caused suppression of proliferative T-cell responses on day 7 post infection (pi). The ΔORF1/ORF2 virus caused significantly shorter primary pyrexia and significantly reduced nasal shedding, and an attenuated decrease in PBMC IL-8 as well as increased Tbet responses compared to WT-infected ponies. In conclusion, our findings are (i) that infection of ponies with EHV-1 leads to modulation of immune responses, which are correlated with disease pathogenesis, and (ii) that the ORF1/2 genes are of importance for disease outcome and modulation of cytokine responses.
    Veterinary Research 02/2011; 42(1):23. DOI:10.1186/1297-9716-42-23 · 2.82 Impact Factor
  • Source
    • "Indeed, we observed that isolates with the D 752 genotype had significantly more single EHV-1-infected cells below the BM than isolates with the N 752 genotype, at 48 h p.i. This is in agreement with several other studies, showing a more robust replication of neurovirulent D 752 isolates, as shown by a higher level of viraemia of infected cells in the blood (Allen & Breathnach, 2006; Goodman et al., 2006, 2007; Allen, 2008; Van de Walle et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Equine herpesvirus type 1 (EHV-1) is the causative agent of equine herpes myeloencephalopathy, of which outbreaks are reported with increasing frequency throughout North America and Europe. This has resulted in its classification as a potentially emerging disease by the US Department of Agriculture. Recently, it was found that a single nucleotide polymorphism (SNP) in the viral DNA polymerase gene (ORF30) at aa 752 (N-->D) is associated with the neurovirulent potential of EHV-1. In the present study, equine respiratory mucosal explants were inoculated with several Belgian isolates typed in their ORF30 as D(752) or N(752), to evaluate a possible difference in replication in the upper respiratory tract. In addition, to evaluate whether any observed differences could be attributed to the SNP associated with neurovirulence, the experiments were repeated with parental Ab4 (reference neurovirulent strain), parental NY03 (reference non-neurovirulent strain) and their N/D revertant recombinant viruses. The salient findings were that EHV-1 spreads plaquewise in the epithelium, but plaques never cross the basement membrane (BM). However, single EHV-1-infected cells could be observed below the BM at 36 h post-inoculation (p.i.) for all N(752) isolates and at 24 h p.i. for all D(752) isolates, and were identified as monocytic cells and T lymphocytes. Interestingly, the number of infected cells was two to five times higher for D(752) isolates compared with N(752) isolates at every time point analysed. Finally, this study showed that equine respiratory explants are a valuable and reproducible model to study EHV-1 neurovirulence in vitro, thereby reducing the need for horses as experimental animals.
    Journal of General Virology 08/2010; 91(Pt 8):2019-28. DOI:10.1099/vir.0.019257-0 · 3.18 Impact Factor
Show more