Abstract
Vaccination is the most cost effective control measure for Johne¿s disease caused by Mycobacterium avium subspecies paratuberculosis (MAP) but currently available whole cell killed formulations have limited efficacy and are incompatible with the diagnosis of bovine tuberculosis by tuberculin skin test. We have evaluated the utility of a viral delivery regimen of non-replicative human Adenovirus 5 and Modified Vaccinia virus Ankara recombinant for early entry MAP specific antigens (HAV) to show protection against challenge in a calf model and extensively screened for differential immunological markers associated with protection. We have shown that HAV vaccination was well tolerated, could be detected using a differentiation of infected and vaccinated animals (DIVA) test, showed no cross-reactivity with tuberculin and provided a degree of protection against challenge evidenced by a lack of faecal shedding in vaccinated animals that persisted throughout the 7 month infection period. Calves given HAV vaccination had significant priming and boosting of MAP derived antigen (PPD-J) specific CD4+, CD8+ IFN-? producing T-cell populations and, upon challenge, developed early specific Th17 related immune responses, enhanced IFN-? responses and retained a high MAP killing capacity in blood. During later phases post MAP challenge, PPD-J antigen specific IFN-? and Th17 responses in HAV vaccinated animals corresponded with improvements in peripheral bacteraemia. By contrast a lack of IFN-?, induction of FoxP3+ T cells and increased IL-1? and IL-10 secretion were indicative of progressive infection in Sham vaccinated animals. We conclude that HAV vaccination shows excellent promise as a new tool for improving control of MAP infection in cattle.
Highlights
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), a chronic granulomatous inflammation of the intestines primarily in ruminants [1] and which has been linked to Crohn’s disease in humans [2]
Whole cell MAP vaccines contain generic mycobacterial cell wall antigens cross-reactive with tuberculin [11] used in diagnostic testing for bovine tuberculosis caused by Mycobacterium bovis
We show that HAV vaccination was well tolerated, could be detected by Differentiation of Infected from Vaccinated Animals (DIVA) testing, did not cross react with the tuberculin test and provided a high degree of protection against challenge evidenced by a lack of faecal shedding that persisted throughout the 38-week test period
Summary
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), a chronic granulomatous inflammation of the intestines primarily in ruminants [1] and which has been linked to Crohn’s disease in humans [2]. The increasing prevalence of MAP infection in cattle, the associated economic losses and zoonotic potential indicate the need for an effective MAP vaccine as a sustainable and economically viable solution for disease control [3]. Whole cell killed MAP vaccines can improve milk productivity [4] reduce the incidence of [10]. Whole cell MAP vaccines contain generic mycobacterial cell wall antigens cross-reactive with tuberculin [11] used in diagnostic testing for bovine tuberculosis caused by Mycobacterium bovis. Whole cell vaccines have limited value in cattle control programmes given their limited efficacy and their interference with current bovine TB diagnostics, in areas with ongoing endemic bovine tuberculosis [13]
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