Defining protective immune responses in livestock
Lead Research Organisation:
THE PIRBRIGHT INSTITUTE
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
Using mouse and livestock models of viral infection, improved assays will be developed to measure correlates of protection in cattle and pigs. In addition, we will investigate the importance of long-term retention of antigen in germinal centres of lymphoid tissue after infection, in the maintenance of a high titre serological response. The duration of circulating neutralising antibody titres and T cell responses will be measured following infection or immunisation with antigens in different formulations and of different physical characteristics. Specifically, improved assays will be developed to measure the specificity CD4 and CD8 responses in the circulation and at mucosal surfaces.
Planned Impact
unavailable
Organisations
People |
ORCID iD |
| Bryan Charleston (Principal Investigator) |
Publications
Carr B
(2013)
CD4+ T-cell responses to foot-and-mouth disease virus in vaccinated cattle
in Journal of General Virology
Charleston B
(2011)
Understanding foot-and-mouth disease virus early pathogenesis and immune responses.
in Transboundary and emerging diseases
Golde WT
(2011)
Evidence of activation and suppression during the early immune response to foot-and-mouth disease virus.
in Transboundary and emerging diseases
Grant C
(2016)
The B-cell response to foot-and-mouth-disease virus in cattle following vaccination and live-virus challenge
in Journal of General Virology
Grant CF
(2012)
Assessment of T-dependent and T-independent immune responses in cattle using a B cell ELISPOT assay.
in Veterinary research
Grant CFJ
(2017)
The B Cell Response to Foot-and-Mouth Disease Virus in Cattle following Sequential Vaccination with Multiple Serotypes.
in Journal of virology
Guzman E
(2016)
Transduction of skin-migrating dendritic cells by human adenovirus 5 occurs via an actin-dependent phagocytic pathway.
in The Journal of general virology
Hamilton CA
(2017)
Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood.
in Immunology
McLaughlin K
(2011)
Hsp110-mediated enhancement of CD4+ T cell responses to the envelope glycoprotein of members of the family Flaviviridae in vitro does not occur in vivo.
in Clinical and vaccine immunology : CVI
| Description | This programme studied the responses of livestock to endemic and exotic infectious viral diseases. The high resolution of our studies using the natural viral hosts will broadly benefit researchers studying comparative immunology, vaccinology, entomology, and transmission biology. Specifically, our results will have immediate benefit to the broad studies of host-virus interactions and the events that lead to pathology and viral transmission; an area that continues to rapidly increase in effort and impact. Elucidating the immune responses to both pathogens and vaccines offers new opportunities to use the optimal animal model to studies of vaccine design, selection and delivery. Veterinary science also stands to benefit from our detailed understanding protective immune responses. Our research will benefit research within the "One Health" agenda. The ability to perform controlled time course experiments using natural viral hosts enables us to provide valuable data to those studying the outcome of human disease. This is particularly pertinent for the closely related and zoonotic viruses we study, where equivalent experiments in humans are not possible. This comprehensive immunological, clinical and transmission data can also provide powerful animal models to examine the delivery, efficacy and safety of new vaccines. This is an area in which Pirbright has had recent significant successes, working with both vaccine companies and consortia of academics. Modern high-throughput methods, particularly in sequencing and mass spectrometry, will be exploited to gain unprecedented resolution on gene function in natural hosts. We have substantial and well-established links to academic institutes in low and middle-income countries across the world, where many of the diseases and insect vectors that we study are endemic. Our inbred line of Babraham pigs are also emerging as a model for human disease, enabling sophisticated immunological studies on a background of limited genetic variation. The inbred Babraham pigs offer a relatively homogeneous genetic background to reduce confounding variation during these experiments and also have great potential as a biomedical model. To enhance the value of these animals for research we have characterised the MHC genes and confirmed they are homozygous. This has enabled the generation of MHC-peptide tetramers, made in collaboration with Professor Andy Sewell (Cardiff University), which will aid greatly in enumerating and phenotyping influenza specific T cells. This will allow us to use T cell clones as probes to investigate the location and timing of antigen presentation and trace receptor gene usage during immune responses. Among potential candidate vaccine antigens for each pathogen only a minority induce protective immunity. Therefore, the identification of protective B and T cell antigens and epitopes is crucial for vaccine development and for evaluation of their immunogenicity and efficacy. We will identify and characterise T and B cell antigens and epitopes derived from a range of veterinary species and their viral pathogens, focussing on identification of conserved antigenic targets that may provide broad cross-protection. Antigen and epitope mapping approaches will use both well-established techniques, such as ELISA and virus neutralisation assays for screening antibody responses and proliferation, intra-cytoplasmic staining and ELISpot for detection of T cell responses, as well as new computational methods. Cutting-edge technologies such as cryo-electron microscopy and crystallography will be used to structurally define antibody epitopes and bio-layer interferometry and tandem mass spectrometry to define viral peptidomes, presented by MHC molecules. These antigens can then be used with appropriate delivery platforms, such as viral vectors, to determine if they are immunogenic and enhance protective immune responses. |
| Exploitation Route | Through the dissemination of results through established collaborations, dedicated training and targeted conferences and workshops, we will continue to reach out to as wide a group of academic beneficiaries in these countries as possible. The potential academic benefit in these countries is vast, and is an area that Pirbright remains committed to promoting. |
| Sectors | Agriculture Food and Drink Healthcare |
| Description | This work underpins the development of reagents and understanding of immune responses in cattle to investigate pathogenesis and protective immune responses to BVDV and FMDV |
| First Year Of Impact | 2009 |
| Sector | Agriculture, Food and Drink |
| Impact Types | Economic |