| 1. |
- Hägglund, Sara, et al.
(författare)
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Characterization of an Experimental Vaccine for Bovine Respiratory Syncytial Virus
- 2014
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 21:7, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Bovine respiratory syncytial virus (BRSV) and human respiratory syncytial virus (HRSV) are major causes of respiratory disease in calves and children, respectively, and are priorities for vaccine development. We previously demonstrated that an experimental vaccine, BRSV-immunostimulating complex (ISCOM), is effective in calves with maternal antibodies. The present study focuses on the antigenic characterization of this vaccine for the design of new-generation subunit vaccines. The results of our study confirmed the presence of membrane glycoprotein (G), fusion glycoprotein (F), and nucleoprotein (N) proteins in the ISCOMs, and this knowledge was extended by the identification of matrix (M), M2-1, phosphoprotein (P), small hydrophobic protein (SH) and of cellular membrane proteins, such as the integrins alpha(V)beta(1), alpha(V)beta(3), and alpha(3)beta(1). The quantity of the major protein F was 4- to 5-fold greater than that of N (similar to 77 mu g versus similar to 17 mu g/calf dose), whereas G, M, M2-1, P, and SH were likely present in smaller amounts. The polymerase (L), M2-2, nonstructural 1 (NS1), and NS2 proteins were not detected, suggesting that they are not essential for protection. Sera from the BRSV-ISCOM-immunized calves contained high titers of IgG antibody specific for F, G, N, and SH. Antibody responses against M and P were not detected; however, this does not exclude their role in protective T-cell responses. The absence of immunopathological effects of the cellular proteins, such as integrins, needs to be further confirmed, and their possible contribution to adjuvant functions requires elucidation. This work suggests that a combination of several surface and internal proteins should be included in subunit RSV vaccines and identifies absent proteins as potential candidates for differentiating infected from vaccinated animals.
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| 2. |
- Riihimäki, Miia, et al.
(författare)
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Viral load of equine herpesviruses 2 and 5 in nasal swabs of actively racing Standardbred trotters: Temporal relationship of shedding to clinical findings and poor performance
- 2015
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Ingår i: Veterinary Microbiology. - : Elsevier BV. - 0378-1135 .- 1873-2542. ; 179, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- The equine gamma herpesviruses 2 and 5 (EHV-2 and -5) have frequently been observed in the equine population and until recently presumed low to nonpathogenic. However, recent reports linking presence of equine gamma herpesviruses with clinical signs of mild to severe lung disease, suggest that the role of these viruses in respiratory disease and poor performance syndrome is still unclear. Moreover, baseline data regarding the temporal pattern of shedding of EHV-2 and EHV-5 within stables and within individual actively racing horses have been lacking. In a prospective longitudinal study, we followed elite racing Standardbred trotters at monthly intervals for 13 months, to investigate whether the amount of EHV-2 and EHV-5 shedded in nasal secretions varied over time within and between individual horses. Sixty-six elite horses were investigated by analyzing nasal swabs and serum samples, a health check and evaluation of athletic performance monthly during the study period. Nasal swabs were analyzed with two newly developed qPCR assays for EHV-2 and EHV-5, respectively. Of 663 samples, 197 (30%) were positive for EHV-2 and 492(74%) positive for EHV-5. Furthermore, 176(27%) of the samples were positive for both EHV-2 and EHV-5 simultaneously. There was considerable variation in the amount and frequency of shedding of EHV-2 and EHV-5 within and between individual horses. Viral load varied seasonally, but neither EHV-2 nor EHV-5 viral peaks were associated with clinical respiratory disease and/or poor performance in racing Standardbred trotters. (C) 2015 Elsevier B.V. All rights reserved.
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| 3. |
- Blodörn, Krister, et al.
(författare)
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A bovine respiratory syncytial virus model with high clinical expression in calves with specific passive immunity
- 2015
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Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle worldwide. Calves are particularly affected, even with low to moderate levels of BRSV-specific maternally derived antibodies (MDA). Available BRSV vaccines have suboptimal efficacy in calves with MDA, and published infection models in this target group are lacking in clinical expression. Here, we refine and characterize such a model. Results In a first experiment, 2 groups of 3 calves with low levels of MDA were experimentally inoculated by inhalation of aerosolized BRSV, either: the Snook strain, passaged in gnotobiotic calves (BRSV-Snk), or isolate no. 9402022 Denmark, passaged in cell culture (BRSV-Dk). All calves developed clinical signs of respiratory disease and shed high titers of virus, but BRSV-Snk induced more severe disease, which was then reproduced in a second experiment in 5 calves with moderate levels of MDA. These 5 calves shed high titers of virus and developed severe clinical signs of disease and extensive macroscopic lung lesions (mean+/−SD, 48.3+/−12.0% of lung), with a pulmonary influx of inflammatory cells, characterized by interferon gamma secretion and a marked effect on lung function. Conclusions We present a BRSV-infection model, with consistently high clinical expression in young calves with low to moderate levels of BRSV-specific MDA, that may prove useful in studies into disease pathogenesis, or evaluations of vaccines and antivirals. Additionally, refined tools to assess the outcome of BRSV infection are described, including passive measurement of lung function and a refined system to score clinical signs of disease. Using this cognate host calf model might also provide answers to elusive questions about human RSV (HRSV), a major cause of morbidity in children worldwide.
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| 4. |
- Chanrot, Metasu, et al.
(författare)
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Bovine herpes virus type 4 alters TNF-α and IL-8 profiles and impairs the survival of bovine endometrial epithelial cells
- 2017
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Ingår i: Reproductive Biology. - : Elsevier BV. - 1642-431X .- 2300-732X. ; 17, s. 225-232
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Tidskriftsartikel (refereegranskat)abstract
- Bovine herpes virus type 4 (BoNV-4) can be transmitted by contaminated semen to cows at the time of breeding and may cause uterine disease. The aim of this study was to characterize the susceptibility of bovine endometrial epithelial cells (bEEC) to BoHV-4 by using an in vitro model. When bEEC were challenged with different multiplicity of infection (MOI; from 0.001 to 10) of BoHV-4 for 6 days, a significant decrease in cell survival with increasing MOI was observed. The bEEC were subsequently challenged with BoNV-4 MOI 0.1 for 7 days. During the first 4 days, numbers increased in a similar way in controls and infected group (p < 0.01 when compared to Day 0). After Day 4, numbers of live cells in infected samples decreased when compared to controls and were lower than control at Day 7 (p < 0.01). From titration and qPCR, increasing number of viral particles was observed from Day 1, and reached a plateau at Day 5. Concentrations of IL-8 increased with time and were higher in supernatants from infected cells than in controls (p < 0.0001). TNF-alpha concentrations presented similar profile as cell survival ones. In conclusion, the survival of bEEC was strongly impaired by BoNV-4 infection in a time and dose dependent manner and supernatant cytokine profiles were altered. This information supports BoHV-4 implication in clinical cases of uterine diseases and the existence of a risk of BoNV-4 transmission from infected males through animal breeding. (C) 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Sp. z o.o. All rights reserved.
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| 5. |
- Hägglund, Sara, et al.
(författare)
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Pathogenesis, Host Innate Immune Response, and Aerosol Transmission of Influenza D Virus in Cattle
- 2019
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 93
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Tidskriftsartikel (refereegranskat)abstract
- The recently discovered influenza D virus (IDV) of the Orthomyxoviridae family has been detected in swine and ruminants with a worldwide distribution. Cattle are considered to be the primary host and reservoir, and previous studies suggested a tropism of IDV for the upper respiratory tract and a putative role in the bovine respiratory disease complex. This study aimed to characterize the pathogenicity of IDV in naive calves as well as the ability of this virus to transmit by air. Eight naive calves were infected by aerosol with a recent French isolate, D/bovine/France/5920/2014. Results show that IDV replicates not only in the upper respiratory tract but also in the lower respiratory tract (LRT), inducing moderate bronchopneumonia with restricted lesions of interstitial pneumonia. Inoculation was followed by IDV-specific IgG1 production as early as 10 days postchallenge and likely both Th1 and Th2 responses. Study of the innate immune response in the LRT of IDV-infected calves indicated the overexpression of pathogen recognition receptors and of chemokines CCL2, CCL3, and CCL4, but without overexpression of genes involved in the type I interferon pathway. Finally, virological examination of three aerosol-sentinel animals, housed 3 m apart from inoculated calves (and thus subject to infection by aerosol transmission), and IDV detection in air samples collected in different areas showed that IDV can be airborne transmitted and infect naive contact calves on short distances. This study suggests that IDV is a respiratory virus with moderate pathogenicity and probably a high level of transmission. It consequently can be considered predisposing to or a cofactor of respiratory disease.IMPORTANCE Influenza D virus (IDV), a new genus of the Orthomyxoviridae family, has a broad geographical distribution and can infect several animal species. Cattle are so far considered the primary host for IDV, but the pathogenicity and the prevalence of this virus are still unclear. We demonstrated that under experimental conditions (in a controlled environment and in the absence of coinfecting pathogens), IDV is able to cause mild to moderate disease and targets both the upper and lower respiratory tracts. The virus can transmit by direct as well as aerosol contacts. While this study evidenced overexpression of pathogen recognition receptors and chemokines in the lower respiratory tract, IDV-specific IgG1 production as early as 10 days postchallenge, and likely both Th1 and Th2 responses, further studies are warranted to better understand the immune responses triggered by IDV and its role as part of the bovine respiratory disease complex.
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| 6. |
- Leijon, Mikael, et al.
(författare)
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Genetic variation and Dynamics of infections of equine herpesvirus type 5 in individual horses
- 2016
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 97, s. 169-178
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Tidskriftsartikel (refereegranskat)abstract
- Equid herpesvirus 5 (EHV-5) is related to the human Epstein-Barr virus (human herpesvirus 4) and has frequently been observed in equine populations worldwide. EHV-5 was previously assumed to be low to non-pathogenic; however, studies have also related the virus to the severe lung disease equine multinodular pulmonary fibrosis (EMPF). Genetic information of EHV-5 is scanty: the whole genome was recently described and only limited nucleotide sequences are available. In this study, samples were taken twice 1 year apart from eight healthy horses at the same professional training yard and samples from a ninth horse that was diagnosed with EMPF with samples taken pre- and post-mortem to analyse partial glycoprotein B (gB) gene of EHV-5 by using next-generation sequencing. The analysis resulted in 27 partial gB gene sequences, 11 unique sequence types and five amino acid sequences. These sequences could be classified within four genotypes (I-IV) of the EHV-5 gB gene based on the degree of similarity of the nucleotide and amino acid sequences, and in this work horses were shown to be identified with up to three different genotypes simultaneously. The observations showed a range of interactions between EHV-5 and the host over time, where the same virus persists in some horses, whereas others have a more dynamic infection pattern including strains from different genotypes. This study provides insight into the genetic variation and dynamics of EHV-5, and highlights that further work is needed to understand the EHV-5 interaction with its host.
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| 7. |
- Malmsten, Anna, et al.
(författare)
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Serological testing of Schmallenberg virus in Swedish wild cervids from 2012 to 2016
- 2017
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Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Schmallenberg virus (SBV) first emerged in Europe in 2011, and in Sweden in late 2012. The virus was still circulating in parts of Europe in 2015. In recent testing, the virus has not been detected in Swedish domestic animals, indicating that it is no longer circulating in Sweden. It is not known if the virus has circulated and is still circulating in Swedish wild cervid populations and whether wildlife can act as virus reservoirs. The aim of this study was to investigate whether SBV has circulated, and is still circulating among wild cervids in Sweden.Results: Ninety-two sera from moose (Alces alces, n = 22), red deer (Cervus elaphus, n = 15), fallow deer (Dama dama, n = 44), and roe deer (Capreolus capreolus, n = 11) were collected and analyzed for antibodies against SBV. The sampling occurred in the southern and middle part of Sweden during three time periods: 1) before the vector season in 2012, 2) after the vector season in 2012, and 3) after the vector season in 2015. Animals from periods 1 and 2 were of varying ages, whereas animals collected in period 3 were born after the vector season 2013. Animals from period 1 (n = 15) and 3 (n = 47) were seronegative, but, 53% (16 of 30) of animals from period 2 were seropositive, determined by SBV competitive ELISA. Samples from period 2 were additionally analyzed for SBV-neutralizing antibodies. Such antibodies were detected in 16/16 SBV-N-antibody-positive, 3/12 negative and 2/2 doubtful sera. The two tests were in accordance at SBV-neutralizing antibody titers of 1:32 or higher.Conclusion: Our results show that SBV circulated among wild cervids during the vector season of 2012. Three years later, no SBV-antibodies were detected in animals born after the vector season 2013. The likely absence of SBV circulation in Sweden, in contrast to other parts of Europe, might be explained by the annual occurrence of a vector-free season due to climate conditions. Interpretations are limited by the small sample-size, but the results suggest that the SBV competitive ELISA has high specificity but might have slightly lower sensitivity compared to a seroneutralization assay, when using samples from wild cervids.
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| 8. |
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| 9. |
- Anderson, Jenna, et al.
(författare)
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Evaluation of the Immunogenicity of an Experimental Subunit Vaccine That Allows Differentiation between Infected and Vaccinated Animals against Bluetongue Virus Serotype 8 in Cattle
- 2013
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 20, s. 1115-1122
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Tidskriftsartikel (refereegranskat)abstract
- Bluetongue virus (BTV), the causative agent of bluetongue in ruminants, is an emerging virus in northern Europe. The 2006 out-break of BTV serotype 8 (BTV-8) in Europe was marked by an unusual teratogenic effect and a high frequency of clinical signs in cattle. Conventional control strategies targeting small ruminants were therefore extended to include cattle. Since cattle were not routinely vaccinated before 2006, the immune responses to BTV have not been studied extensively in this species. With the aims of developing a subunit vaccine against BTV-8 for differentiation between infected and vaccinated animals based on viral protein 7 (VP7) antibody detection and of improving the current understanding of the immunogenicity of BTV proteins in cattle, the immune responses induced by recombinant VP2 (BTV-8) and nonstructural protein 1 (NS1) and NS2 (BTV-2) were studied. Cows were immunized twice (with a 3-week interval) with the experimental vaccine, a commercial inactivated vaccine, or a placebo. The two vaccines induced similar neutralizing antibody responses to BTV-8. Furthermore, the antibody responses detected against VP2, NS1, and NS2 were strongest in the animals immunized with the experimental vaccine, and for the first time, a serotype cross-reactive antibody response to NS2 was shown in cattle vaccinated with the commercial vaccine. The two vaccines evoked measurable T cell responses against NS1, thereby supporting a bovine cross-reactive T cell response. Finally, VP7 sero-conversion was observed after vaccination with the commercial vaccine, as in natural infections, but not after vaccination with the experimental vaccine, indicating that the experimental vaccine may allow the differentiation of vaccinated animals from infected animals regardless of BTV serotype. The experimental vaccine will be further evaluated during a virulent challenge in a high-containment facility.
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| 10. |
- Anderson, Jenna, et al.
(författare)
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Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle
- 2014
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1358-8745. ; 32, s. 6614-6621
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Tidskriftsartikel (refereegranskat)abstract
- Bluetongue virus (BTV) infections in ruminants pose a permanent agricultural threat since new serotypes are constantly emerging in new locations. Clinical disease is mainly observed in sheep, but cattle were unusually affected during an outbreak of BTV seroype 8 (BTV-8) in Europe. We previously developed an experimental vaccine based on recombinant viral protein 2 (VP2) of BTV-8 and non-structural proteins 1 (NS1) and NS2 of BTV-2, mixed with an immunostimulating complex (ISCOM)-matrix adjuvant. We demonstrated that bovine immune responses induced by this vaccine were as good or superior to those induced by a classic commercial inactivated vaccine. In this study, we evaluated the protective efficacy of the experimental vaccine in cattle and, based on the detection of VP7 antibodies, assessed its DIVA compliancy following virus challenge. Two groups of BTV-seronegative calves were subcutaneously immunized twice at a 3-week interval with the subunit vaccine (n=6) or with adjuvant alone (n=6). Following BTV8 challenge 3 weeks after second immunization, controls developed viremia and fever associated with other mild clinical signs of bluetongue disease, whereas vaccinated animals were clinically and virologically protected. The vaccine-induced protection was likely mediated by high virus-neutralizing antibody titers directed against VP2 and perhaps by cellular responses to NS1 and NS2. T lymphocyte responses were cross-reactive between BTV-2 and BTV-8, suggesting that NS1 and NS2 may provide the basis of an adaptable vaccine that can be varied by using VP2 of different serotypes. The detection of different levels of VP7 antibodies in vaccinated animals and controls after challenge suggested a compliancy between the vaccine and the DIVA companion test. This SW subunit vaccine is a promising candidate that should be further evaluated and developed to protect against different serotypes. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
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