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

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.