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Proof of concept studies in animals

Extensive preclinical studies of the vaccine were carried out in MAP-infected mice at a number of dose levels and prime/boost configurations and with various vectors. None of the HAV-vaccinated mice suffered any detectable adverse effect. HAV-vaccination in all vector combinations was immunogenic, inducing T-cells reactive against the vaccine antigens, and achieving significant reductions in MAP loads compared to the controls.

The vaccine was also trialled in a prime/boost configuration involving human adenovirus (hAd5) and modified vaccinia Ankara (MVA) vectors in a 3 year BBSRC-funded study in healthy male calves. Again, no adverse results were seen in the HAV-vaccinated animals. MAP-specific cellular immune responses were seen in the HAV-vaccinated animals, but not the controls, within two weeks of boosting. All the HAV-vaccinated animals became MAP negative in blood, and faecal shedding was abolished. These effects continued through to termination 9 months later. Tissue samples on autopsy showed similar results for reduction in MAP load. This efficacy against MAP greatly exceeds that of any previous anti-MAP vaccine used to treat Johne’s disease.

An important finding of this work was that HAV vaccination specifically reversed the immune dysregulation imposed by MAP and therefore has the potential to be a powerful and long lasting disease modifier in CD treatment and prevention.