Veterinary Laboratories Agency Weybridge

Addlestone, United Kingdom

Veterinary Laboratories Agency Weybridge

Addlestone, United Kingdom
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Jones G.J.,Veterinary Laboratories Agency Weybridge | Gordon S.V.,Veterinary Laboratories Agency Weybridge | Gordon S.V.,University College Dublin | Hewinson R.G.,Veterinary Laboratories Agency Weybridge | Vordermeier H.M.,Veterinary Laboratories Agency Weybridge
Infection and Immunity | Year: 2010

Results of previous studies utilizing bioinformatic approaches in antigen-mining experiments revealed that secreted proteins are among the most frequently recognized antigens from Mycobacterium bovis. Thus, we hypothesized that the analysis of secreted proteins is likely to reveal additional immunogenic antigens that can be used to increase the specificity of diagnostic tests or be suitable vaccination candidates for mycobacterial infections. To test this hypothesis, 382 pools of overlapping peptides spanning 119 M. bovis secreted and potentially secreted proteins were screened for the ability to stimulate a gamma interferon response in vitro using whole blood from tuberculin-positive reactor (TB reactor) cattle. Of the 119 proteins screened, 70 (59%) induced positive responses in the TB reactor animals to various degrees. Strikingly, all but one of the 15 ESAT-6 proteins tested were recognized by at least 30% of the TB reactor animals, with 12 of the 22 most commonly recognized antigens belonging to this protein family. Further analysis of these data demonstrated that there was no significant difference in immunogenicity between the ESAT-6 proteins that were components of potentially intact ESX secretory systems and those corresponding to additional partial esx loci. Importantly for vaccine design, antigenic epitopes in some highly conserved regions shared by numerous ESAT-6 proteins were identified. However, despite this considerable homology, peptide-mapping experiments also revealed that immunodominant peptides were located in regions of amino acid variability. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Over the last 20 years, pig production has been characterised by a rapid increase in the volume of pig meat produced, greater intensification of the pig-rearing process and much greater international movement of products. There have also been many novel viral diseases that challenge the industry. Are these two developments linked and, if so, how? To understand how changes in the industry may influence the evolution of viruses, it is important to understand something of evolutionary theory. For RNA viruses, the concept of 'quasispecies' has moved solidly from theory to fact. Such viruses do not exist as a single entity, but as a 'cloud' of viruses, whose degree of diversity is influenced by a number of factors. Chief among these are the size and rate of the replicating population, along with the availability and diversity of susceptible hosts. A feature of RNA viruses is a high level of mutation, due to lack of capability to correct errors on the part of the host cell. Both in vivo and in vitro, RNA viruses have been shown to accumulate and fix these mutations, leading to bottleneck events and fitness loss, the phenomenon known as 'Muller's ratchet'. Likewise, the opposite effect, fitness gain, can be achieved in an environment providing for high levels of replication and the generation of large populations of virus. This has been shown to be possible in vitro by high-volume passage. It is possible that the regular introduction of diverse viruses within large-scale pig production provides an in vivo equivalent that could drive quasispecies populations to increased fitness, and may explain why emergent viruses, either new to science or with new synergies and presentation, seem to be appearing more commonly.

Wales A.D.,Veterinary Laboratories Agency Weybridge | Cook A.J.C.,Veterinary Laboratories Agency Weybridge | Davies R.H.,Veterinary Laboratories Agency Weybridge
Veterinary Record | Year: 2011

Salmonella infection in pig production is typically endemic and largely asymptomatic. It is a cause of substantial concern among food safety bodies, prompting voluntary and legislative responses aimed at monitoring and reducing the number of Salmonella-infected animals entering the human food chain. Elimination of the problem at an early stage of production is highly desirable, and to this end the present review examines published evidence on the carriage of Salmonella by piglets before and after weaning, as well as evidence on the dynamics of Salmonella infection in the weaner and grower stages of pig production, the effects of maternal immunity, and risk factors for Salmonella excretion after weaning. Various interventions to reduce or eliminate Salmonella infection in young pigs have been tried, such as vaccination, competitive exclusion, treatments in feed and water, antibiotic administration, disinfection of animals, and segregated weaning to clean accommodation. The evidence on the effectiveness of these is considered, and the last is examined in some detail, as it appears currently to offer the best chance of eliminating Salmonella from growing stock.

Beck K.E.,Veterinary Laboratories Agency Weybridge | Sallis R.E.,Veterinary Laboratories Agency Weybridge | Lockey R.,Veterinary Laboratories Agency Weybridge | Simmons M.M.,Veterinary Laboratories Agency Weybridge | Spiropoulos J.,Veterinary Laboratories Agency Weybridge
Journal of Neuropathology and Experimental Neurology | Year: 2010

It is currently believed that primary transmission of classical scrapie to wild-type mice is inefficient and characterized by low attack rates and variable incubation periods and lesion profiles. Consequently, strain characterization of classical scrapie in these mice relies on subpassage. The aim of this study was to perform a retrospective analysis of lesion profiles and immunohistochemistry patterns after transmission of a large number of classical scrapie sources to wild-type mice and to investigate trends that might be used to characterize the agent without subpassaging. Scrapie field cases (n = 31) collected from individual farms between 1996 and 1999 were inoculated into RIII, C57BL, and VM mice and profiled using standard methodology and analyzed by immunohistochemistry. Using cluster analysis to resultant lesion profiles produced groups of similar lesion profiles in RIII and C57BL mice. We observed correlations between lesion profile clusters and the ovine prion protein (PrP) genotype. Immunohistochemistry indicated donor-mediated trendssc in the PrP pattern. These results indicate that ovine PrPsc genotype is a factor that is linked to both the lesion profile and the pattern of PrP deposition on primary transmission of classical scrapie to wild-type mice. © 2010 by the American Association of Neuropathologists, Inc.

Howard W.A.,Veterinary Laboratories Agency Weybridge | Essen S.C.,Veterinary Laboratories Agency Weybridge | Strugnell B.W.,Veterinary Laboratories Agency Thirsk | Russell C.,Veterinary Laboratories Agency Weybridge | And 3 more authors.
Emerging Infectious Diseases | Year: 2011

Surveillance for influenza virus in pigs in the United Kingdom during spring 2010 detected a novel reassortant influenza virus. This virus had genes encoding internal proteins from pandemic (H1N1) 2009 virus and hemagglutinin and neuraminidase genes from swine influenza virus (H1N2). Our results demonstrate processes contributing to influenza virus heterogeneity.

Randall L.P.,Veterinary Laboratories Agency Weybridge | Clouting C.,Veterinary Laboratories Agency Weybridge | Horton R.A.,Veterinary Laboratories Agency Weybridge | Coldham N.G.,Veterinary Laboratories Agency Weybridge | And 4 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2011

Objectives: To determine the prevalence of extended-spectrum β-lactamases (ESBLs) in Escherichia coli from poultry in Great Britain (GB). Methods: E. coli was isolated from 388 broiler chicken caecal samples from 22 abattoirs and from boot swabs from 442 turkey flocks over successive 1 year periods. CHROMagar ECC with and without cephalosporin antibiotics was used as isolation medium and the chicken study also used CHROMagar CTX. ESBL phenotype iso- lates were tested for the presence of blaCTX-M, blaOXA, blaSHV, blaTEM and ampC genes. CTX-M isolates were tested for O25 serogroup, replicon, CTX-M sequence, multilocus sequence type (MLST), PFGE type, plasmid transfer and qnrA, qnrB, qnrS, qepA and aac(6′)-Ib genes. Results: CTX-M-carrying E. coli were isolated from 54.5% of the broiler abattoirs and from 3.6% of individual broiler caecal samples and were CTX-M sequence types 1 (mainly), 3 and 15 with replicon types I1-γ, A/C and P/F, and I1-γ, respectively. CTX-M-carrying E. coli were isolated from 5.2% of turkey meat production farms and 6.9% of turkey breeder farms and were CTX-M sequence types 1, 14 (mainly), 15 and 55 with mainly replicon types F, FIA, K and I1-γ, respectively. None of the CTX-M isolates was serogroup O25. PFGE/MLST showed the CTX-M isolates to be clonally diverse, although MLST 156 with CTX-M-15 was isolated from both chickens and turkeys and has been previously reported in gulls. CTX-M-negative, ESBL- and blaTEM-positive strains were mainly TEM-52C. Conclusions: Poultry-derived CTX-M E. coli in GB are different from major CTX-M sequence types causing disease in humans. © Crown 2010.

Brown I.H.,Veterinary Laboratories Agency Weybridge
Avian Diseases | Year: 2010

Events during the period extending from 2006 to 2009 have been overshadowed by the ongoing panzootic with H5N1 (highly pathogenic notifiable avian influenza [HPNAI]), which has afflicted 63 countries and three continents (Africa, Asia, and Europe) during the review period. Two countries, Indonesia and Egypt, have formally declared the disease endemic to the World Organisation for Animal Health, while others have used a variety of approaches aimed at containment, control, and eradication. These approaches have achieved variable success, but in 2009 several countries that had previously declared themselves free of HPNAI became reinfected. In addition, the virus continued to be detected widely in wild bird populations, even in the absence of local poultry outbreaks. Other poultry outbreaks with HPNAI have been reported in South Africa (in ostriches with H5N2 in 2006) and the U.K. (in chickens with H7N7 in 2008). Also notable was the report of H5N2 HPNAI in wild bird populations in North Africa in 2007. Improved active surveillance systems and vigilance for notifiable avian influenza (NAI) in domestic poultry, especially in host groupings, in which clinical signs following infection may be inapparent (e.g., domestic waterfowl), have inevitably resulted in the detection and reporting of other activity. Low pathogenicity NAI H5 or H7 viruses were isolated/detected from poultry in Belgium (H5N2, 2008), Chinese Taipei (H5N2, 2008), Denmark (H5N2, 2006; H7N1, 2008), France (H5N2, 2007), Germany (H7N3, 2008), Italy (H7N7, 2006; H7N3, 2007-08), the Netherlands (H7N7, 2006), Portugal (H5N2, 2007; H5N3, 2007), the Republic of Korea (H7N8, 2007; H5N2, 2008), and the U.K. (H7N3, 2006; H7N2, 2007). In addition, there has also been significant activity with H6 and H9 viruses in poultry populations, especially in Asia. © 2010 American Association of Avian Pathologists.

Johnson N.,Veterinary Laboratories Agency Weybridge | Cunningham A.F.,University of Birmingham | Fooks A.R.,Veterinary Laboratories Agency Weybridge
Vaccine | Year: 2010

Infection with rabies virus causes encephalitis in humans that has a case fatality rate of almost 100%. This inability to resolve infection is surprising since both pre-exposure vaccination and, if given promptly, post-exposure vaccination is highly effective at preventing encephalitic disease. The principal immunological correlate of protection produced by vaccination is neutralizing antibody. T-helper cells contribute to the development of immunity whereas cytotoxic T cells do not appear to play a role in protection and may actually be detrimental to the host. One reason for a failure to protect in humans may be the poor immunological response the virus provokes, despite the period between exposure to virus and the development of disease being measured in months. Few individuals have measurable neutralizing antibody on presentation with disease, although in many cases this develops as symptoms become more severe. Furthermore, when antibody is detected in serum it rarely appears in cerebrospinal fluid suggesting limited penetration into the CNS, the site where it is most needed. The role of the modest mononuclear cell infiltrate into the brain parenchyma is unclear. Some studies suggest the virus can suppress cell-mediated immunity early during the infection although there is little mechanistic evidence to support this beyond suppression of intracellular interferon production by the viral phosphoprotein. In contrast, levels of antibody in the CNS correlate to the peak virus production within the CNS. Here we review the current understanding of immune responses to rabies infection and vaccination against this disease. This article identifies a need to understand how rabies antigens are initially presented and how this can influence the subsequent development of antibody responses. This could help identify ways in which the response to prophylactic vaccination can be enhanced and how the natural immune response to infection can be boosted to combat neuroinvasion. Crown Copyright © 2010.

Chalmers R.M.,Singleton Hospital | Smith R.,Veterinary Laboratories Agency Weybridge | Elwin K.,Singleton Hospital | Clifton-Hadley F.A.,UK Environment Agency | Giles M.,UK Environment Agency
Epidemiology and Infection | Year: 2011

In order to monitor epidemiological trends, Cryptosporidium-positive samples (n=4509) from diarrhoeic patients were typed. Compared to the previous 4 years, the proportion of Cryptosporidium hominis cases in 2004-2006 increased to 57·3%, while 38·5% were C. parvum. The remaining 4·2% cases included mixed C. parvum and C. hominis infections, C. meleagridis, C. felis, C. ubiquitum and a novel genotype. When the typing results were combined with enhanced surveillance data to monitor risk exposures, C. hominis was linked to urban dwelling, previous diarrhoea in the household, any travel especially abroad, and using a swimming or paddling pool. C. parvum was linked to having a private water supply, contact with surface water, visiting or living on a farm, and contact with farm animal faeces. The proportion of laboratory-confirmed indigenous cases acquired from direct contact with farm animals was estimated to be 25% for C. parvum and 10% of all reported Cryptosporidium cases. © Copyright Cambridge University Press 2010.

Jones G.J.,Veterinary Laboratories Agency Weybridge | Hewinson R.G.,Veterinary Laboratories Agency Weybridge | Vordermeier H.M.,Veterinary Laboratories Agency Weybridge
Clinical and Vaccine Immunology | Year: 2010

To date, the most promising vaccination strategies for the control of bovine tuberculosis (TB) focus on improving the efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG). However, vaccination with BCG results in sensitization of animals to bovine tuberculin and compromises tests currently used for diagnosis of bovine TB infection. Thus, the development of specific diagnostic reagents capable of discriminating between infected and uninfected vaccinated animals (DIVA) is of high priority. To test the hypothesis that M. bovis-secreted proteins are likely to contain immunogenic antigens that can be used to increase the specificity of diagnostic tests, we screened 379 pools of overlapping peptides representing 119 antigens for their ability to stimulate a gamma inferferon (IFN-γ) response in vitro using whole blood from both TB reactor and BCG-vaccinated animals. Peptide pools representing antigens Rv3020c and Rv2346c induced responses in 61% and 57% of the TB reactor animals, respectively, without inducing responses in any BCG-vaccinated animal studied. Furthermore, individual peptides contained within pools recognized by BCG vaccinates were identified that were specific and induced IFN-γ responses in TB reactor animals. From these results, we constructed a cocktail of nine peptides representing multiple antigen targets that was recognized by 54% of TB reactor animals but also failed to induce responses in any BCG-vaccinated animal studied. In summary, we have identified three peptide cocktails for prioritization in larger trials to discriminate between M. bovis infection and BCG vaccination. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

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