Development of a novel subunitvaccine against Mycobacterium avium subspecies paratuberculosis that does not interfere with bovine TB diagnostic

  • Olsen, Ingrid (Project Manager)
  • Strain, Sam (Project Manager)
  • Andersen, Peter (Project Manager)
  • Jungersen, Gregers (Project Manager)

    Project Details


    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
    Effective start/end date01/11/201031/12/2013


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