The project is funded by The Danish Council for Independent research | Technology and Production 11-105822
Project period:
October 2011 – September 2014.
Project participants:
Professor Gregers Jungersen, Project leader, DTU Vet
Senior Scientist Ulla Riber, DTU Vet
Senior Scientist Claus Lundegaard, DTU Systemsbiology
Post doc Dorte Rosenbek Fink, DTU Vet
Immunologist Henriette Cordes, DTU Vet
Danish Summary
Bakterien Lawsonia intracellularis er den hyppigst diagnosticerede årsag til diarré hos slagtesvin i Danmark og er dermed en af de vigtigste årsager til det store antibiotikaforbrug i svineproduktionen. En kommerciel L. intracellularis vaccine nedsætter antibiotikaforbruget og forbedrer tilvæksten, men der ses kun begrænset effekt på smittespredning af bakterien mellem grise og besætninger. Det er derfor nødvendigt at udvikle en forbedret vaccinationsstrategi. DTU Veterinærinstituttet har de senere år gennemført eksperimentelle svineforsøg som viser, at der efter en primær infektion med bakterien kan opnås en total immunitet uden smittespredning overfor efterfølgende L. intracellularis infektion.
Frem for en traditionel afprøvning af forskellige vaccinekandidaters beskyttende effekt vil vi i dette projekt anvende ”omvendt vaccinologi” til at udpege bakterielle proteiner (antigener), som er involveret i den lokale beskyttelse i tarmen.
Ved omvendt vaccinologi manipulerer vi en anden bakterie til at producere et antal relevante Lawsonia proteiner og anvender antistoffer fra de L. intracellularis-beskyttede grise til at udpege netop de proteiner, der i de beskyttede grise har givet dem immunitet.
Projektgruppen består af forskere fra DTU Veterinærinstituttet med viden inden for vaccineudvikling, immunologi, cellebiologi/bakteriologi og molekylærbiologi og forskere med erfaring i bioinformatik fra DTU SystemBiologi.
Aim
The aim of the project is to identify protein antigens, which elicit protective immune responses in pigs and confer immunity to a challenge infection with L. intracellularis. Specifically, we address antigens recognized by antibodies of the IgA isotype and helper T cells in immune pigs. Identification of such protective B and T cell antigens will lead to identification of proteins which can create basis (lead compounds) for better strategies for development of efficient vaccines to L. intracellularis. More efficient vaccines will contribute to increased animal welfare and reduced usage of antibiotics in the food producing pig industry.
Hypotheses
Based on previous studies with experimental infections of pigs with L. intracellularis, we hypothesize that protective immune responses are active at mucosal surfaces and that screening vaccine candidates for reactivity with serum IgA and CD4+ helper T cells will identify L. intracellularis proteins that can be used in future subunit vaccines. In addition, that a combination of in silico predicted secreted or surface-bound immunogenic proteins from the L. intracellularis genome and a cDNA expression library based on recovered L. intracellularis from infected pigs, will provide the relevant proteins for the antibody-based selection process.
Results dissemination
4th European Veterinary Immunology Workshop (EVIW), Edinburgh, Scotland, UK, 2nd – 4th September 2012: Invited speaker Gregers Jungersen: Humoral and cell-mediated immune responses to primary and secondary infection with Lawsonia intracellularis in pigs
Ethical aspects
In the current project, we apply biological material from previously performed experimental infections and from naturally infected farm animals. Compared to traditional vaccine development we thus significantly minimize the use of animals for experiments. Furthermore, the knowledge generated in this project contributes to development of better vaccines for prevention of disease and thereby increased animal welfare and decreased antibiotic consumption.
Relevant publications from the research group
Thakur A, Pedersen LE, Jungersen G. 2012. Immune Markers and Correlates of Protection for Vaccine Induced Immune Responses. Vaccine 30: 4907-20.
Cordes H., Riber, U., Jensen, T.K., and Jungersen, G. 2012. Cell-mediated and humoral immune responses in pigs following primary and challenge-exposure to Lawsonia intracellularis. Veterinary Research 43:9.
Riber, U., Cordes H., Boutrup, T.S., Jensen, T.K., Heegaard, P.M.H. and Jungersen, G. 2011. Primary infection protects pigs against re-infection with Lawsonia intracellularis in experimental challenge studies. Veterinary Microbiology 149: 406-414.
Riber, U., Boesen, H.T., Jakobsen, J.T., Nguyen, L.T.M. and Jungersen, G. 2011. Co-incubation with IL-18 potentiates antigen-specific IFN-γ response in a whole-blood stimulation assay for measurement of cell-mediated immune responses in pigs experimentally infected with Lawsonia intracellularis. Veterinary Immunology and Immunopathology 139: 257-263.
Meeusen, E.N.T., Walker, J., Peters, A., Pastoret, P-P. and Jungersen, G. 2007. Current status of veterinary vaccines. Clinical Microbiology Reviews 20: 489-510.
Boesen, H.T., Jensen, T.K., Møller, K., Nielsen, L.H. and Jungersen, G. 2005. Evaluation of a novel enzyme-linked immunosorbent assay for serological diagnosis of porcine proliferative enteropathy. Veterinary Microbiology 109: 105-112.
Boesen, H.T., Jensen, T.K., Jungersen, G., Riber, U., Boye, M., and Møller, K. 2005. Development, characterization and diagnostic application of a monoclonal antibody specific for a proteinase K resistant Lawsonia intracellularis antigen. Veterinary Microbiology 105: 199-206.