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

ArticleinVaccine 24(17):3636-45 · May 2006with29 Reads
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.
    • "None of these above mentioned vaccine studies used the same vaccine as tested here. The isotype response to the inactivated vaccine in our current study showed a marked similarity to the induced isotype response pattern after experimental EHV-1 infection , which is dominated by IgG1 and IgG4/7 [6,9]. These results suggest that IgG isotype responses after vaccination may differ depending on the commercial vaccine used. "
    [Show abstract] [Hide abstract] ABSTRACT: Equine herpesvirus type 1 (EHV-1) continues to cause severe outbreaks of abortions or myeloencephalopathy in horses despite widely used vaccination. The aim of this work was to determine the effects of frequent vaccination with an inactivated EHV vaccine on immune development in horses. Fifteen EHV-1 naïve mares were vaccinated a total of 5 times over a period of 8 months with intervals of 20, 60, 90 and 60 days between vaccine administrations. Total antibody and antibody isotype responses were evaluated with a new sensitive EHV-1 Multiplex assay to glycoprotein C (gC) and gD for up to 14 months after initial vaccination. Antibodies peaked after the first two vaccine doses and then declined despite a third administration of the vaccine. The fourth vaccine dose was given at 6 months and the gC and gD antibody titers increased again. Mixed responses with increasing gC but decreasing gD antibody values were observed after the fifth vaccination at 8 months. IgG4/7 isotype responses mimicked the total Ig antibody production to vaccination most closely. Vaccination also induced short-lasting IgG1 antibodies to gC, but not to gD. EHV-1-specific cellular immunity induced by vaccination developed slower than antibodies, was dominated by IFN-γ producing T-helper 1 (Th1) cells, and was significantly increased compared to pre-vaccination values after administration of 3 vaccine doses. Decreased IFN-γ production and reduced Th1-cell induction were also observed after the second and fourth vaccination. Overall, repeated EHV vaccine administration did not always result in increasing immunity. The adverse effects on antibody and cellular immunity that were observed here when the EHV vaccine was given in short intervals might in part explain why EHV-1 outbreaks are observed worldwide despite widely used vaccination. The findings warrant further evaluation of immune responses to EHV vaccines to optimize vaccination protocols for different vaccines and horse groups at risk.
    Full-text · Article · Sep 2015
    • "It also seems to be discrepant that pre-existing maternal antibodies in foals should be able to inhibit antibody production, while pre-existing antibodies in an adult horse do not interfere with vaccination as long as the adult horses are not hypervaccinated. In other words, a vaccine boost in a normal adult horse will result in an antibody increase in addition to pre-existing antibodies to the same pathogen [44,45]. Very likely the reasons for the low antibody response of young foals to traditional vaccine formulations, are more complex than just a passive or inhibitory interference of maternal Ig with endogenous antibody production and differences in adult and foal T cell responses may contribute to the poor outcomes of vaccinating young foals. "
    [Show abstract] [Hide abstract] ABSTRACT: The development of equine immunity from the fetus to adulthood is complex. The foal's immune response and the immune mechanisms that they are equipped along with changes over the first months of life until the immune system becomes adult-like are only partially understood. While several innate immune responses seem to be fully functional from birth, the onset of adaptive immune response is delayed. For some adaptive immune parameters, such as IgG1, IgG3, IgG5 and IgA antibodies, the immune response starts before or at birth and matures within 3 months of life. Other antibody responses, such as IgG4, IgG7 and IgE production, slowly develop within the first year of life until they reach adult levels. Similar differences have been observed for adaptive T cell responses. Interferon-gamma (IFN-γ) production by T helper 1 (Th1)-cells and cytotoxic T-cells starts shortly after birth with low level production that gradually increases during the first year of life. In contrast, interleukin-4 (IL-4) produced by Th2-cells is almost undetectable in the first 3 months of life. These findings offer some explanation for the increased susceptibility of foals to certain pathogens, such as Rhodococcus equi. The delay in Th-cell development, and in particular Th2 immunity, during the first months of life also provides an explanation for the reduced responsiveness of young horses to most traditional vaccines. In summary, all immune components of adult horses seem to exist in foals but the orchestrating and regulation of the immune response in immature horses is strikingly different. Young foals are fully competent and can perform certain immune responses but many mechanisms have yet to mature. Additional work is needed to improve our understanding of immunity and immune regulation in young horses, to identify the preferred immune pathways that they are using, and to ultimately provide new preventive strategies to protect against infectious disease.
    Article · Nov 2014
    • "Although Traub-Dargatz et al. identified vaccination within 5 weeks of exposure to EHV-1 as a risk factor for the development of EHM, they refrained from drawing any conclusions from this finding and did not give details of the types of vaccines that were administered [9]. Although no vaccine currently claims to protect against the development of EHM, it has been shown that vaccination with a modified-live product may provide increased protection against the development of clinical signs of disease when compared with inactivated vaccines given singly or in combination products [14,15]. Study limitations include the retrospective nature of the study and the small sample size, which did not allow for extensive statistical comparison. "
    [Show abstract] [Hide abstract] ABSTRACT: Reasons for performing the studyData associating quantitative viral load with severity, clinical signs, and survival in equid herpesvirus-1 myeloencephalopathy (EHM) has not been reported.Objectives To report the clinical signs, treatment, temporal progression of viral loads, and survival in seven horses with naturally occurring EHM and to examine these factors’ association with survival.Study designRetrospective case seriesMethods The population included 7 horses with EHM presented to the University of California, Davis William R. Pritchard Veterinary Medical Teaching Hospital from May to September 2011. Horses were graded using a neurologic grading scale. Daily quantitative PCR was performed on nasal secretions and whole blood. Treatment, survival, outcome, and histopathology were reported.ResultsAt presentation, one horse was grade 5/5, 3 were grade 4/5 and 3 were grade 3/5.All were treated with anti-inflammatory drugs, valacyclovir, and management in a sling if necessary. All were infected with equid herpesvirus-1 (EHV-1) of DNA polymerase D752 genotype. Peak viral load in nasal secretions and blood of 5 survivors ranged from 6.9 x 103 – 2.81 x 105 (median 5.11 x 104) and 143- 4,340 gB gene copies/million eukaryotic cells (median 3,146) respectively. The 2 non-survivors presented with grade 3/5 neurologic signs and progressed to encephalopathy. Peak viral load was higher in non-survivors with levels in nasal secretions of 1.9 x 109 and 2.2 x 109 and in blood of 2.05 x 104 and 1.02 x 105 gB gene copies/million eukaryotic cells. Case fatality was 2/7.Conclusions Non-survivors had viral loads 1000-fold higher in nasal secretions and 10-fold higher in blood than survivors. There was no relationship between severity of clinical signs at presentation and survival. Thus encephalopathy and high viral load was negatively associated with survival in this population. Further research should be performed to determine if high viral loads are associated with encephalopathy and poor prognosis.
    Full-text · Article · Sep 2014
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