| Summary: | Johne’s disease (JD) caused by <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> (<i>M. paratuberculosis</i>) is a chronic infection characterized by the development of granulomatous enteritis in wild and domesticated ruminants. It is one of the most significant livestock diseases not only in the USA but also globally, accounting for USD 200–500 million losses annually for the USA alone with potential link to cases of Crohn’s disease in humans. Developing safe and protective vaccines is of a paramount importance for JD control in dairy cows. The current study evaluated the safety, immunity and protective efficacy of a novel live attenuated vaccine (LAV) candidate with and without an adjuvant in comparison to an inactivated vaccine. Results indicated that the LAV, irrespective of the adjuvant presence, induced robust T cell immune responses indicated by proinflammatory cytokine production such as IFN-γ, IFN-α, TNF-α and IL-17 as well as strong response to intradermal skin test against <i>M. paratuberculosis</i> antigens. Furthermore, the LAV was safe with minimal tissue pathology. Finally, calves vaccinated with adjuvanted LAV did not shed <i>M. paratuberculosis</i> post-challenge, a much-desired characteristic of an effective vaccine against JD. Together, this data suggests a strong potential of testing LAV in field trials to curb JD in dairy herds.
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