External Organisations

  • National Veterinary Institute, Norway, Norway
  • Agri-Foods and Biosciences Institute, Ireland
  • Statens Serum Institut, Denmark

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Paratuberculosis is a chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease leads to substantial economic losses and poor animal welfare. The currently available vaccines against paratuberculosis consist of variations of whole bacteria with adjuvants. These vaccines have shown various efficacies in field studies and seem to diminish the clinical symptoms, but they cannot prevent the animals from becoming bacterial shedders. Another major problem of the current vaccines is their interference with surveillance programs and diagnosis of bovine tuberculosis. Animals vaccinated with whole cell paratuberculosis vaccine will produce false-positive test results in screening programs for bovine TB. For these reasons vaccination against paratuberculosis with current vaccines is either not allowed or greatly restricted in many countries. MAP has also been linked to Crohn’s disease in humans and enhanced control of paratuberculosis is therefore likely to have a positive impact on consumer trust in animal products and possibly human health. It is therefore desirable to develop vaccines that prevent spreading of MAP, prevent MAP entering the human food chain and which do not confound diagnostic tests for bovine tuberculosis One strategy for development of new vaccines is to use different antigens in the vaccines and the diagnostic tests, so called DIVA (Differentiation between Infected and Vaccinated Animals) strategy. We suggest exploiting the DIVA principle to develop a new vaccine for MAP that does not interfere with the current bovine TB surveillance program in place in most countries. Furthermore such a vaccine can potentially be used in combination with control program for paratuberculosis. Rather than use full length proteins we suggest using pools of shorter peptides that are specific for MAP. This is done because we can select a much larger number of sequence differences between the two genomes if we identify short (15-18 aminoacids) peptide rather than full length proteins that are unique to MAP. The aim of this project is thus to develop a novel vaccine against paratuberculosis that does not interfere with diagnostic tests for bovine TB and paratuberculosis. To achieve this we will identify potential peptide vaccine candidates using two completely different complementary approaches; in silico mining and MAP derived specific T-cell clones to screen a MAP expression library. Cocktails of specific peptides will be formulated in liposomes with the aim of obtaining maximal peptide absorption or entrapment inside the liposomes. The vaccine candidates will be tested for immunogenicity in mice followed by vaccination and challenge studies in calves. The effect of the vaccine candidates on bovine TB infection and diagnostic tests for bovine TB and paratuberculosis will be assessed. At the end of the study we aim to have a vaccine candidate that can go on to field evaluation.
StatusCurrent
Period01/11/1031/12/13
Financing sourceForsk. EU - Andre EU-midler
Research programmeForsk. EU - Andre EU-midler
Amount2,263,680.00 Danish kroner
Project ID22473
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ID: 2240274