FUNCTIONAL GENOMICS OF JOHNE`S DISEASE: DECIPHERING KINETICS OF EFFECTIVE IMMUNIZATION

<b>Project Methods</b><br> In this project, we will start our efforts by deciphering the safety and immunogenicity of LAV candidates in calves, the target host for JD vaccination. Such analysis will allow us to understand cellular and humoral responses associated with LAV that distinguish them from the licensed, inactivated vaccine (Mycopar). Second, we will examine the kinetics of developmentof protective immunity to LAV to identify mechanisms of and durability of immunity, the key factors for a successful national strategy to control JD in dairy cattle. Third, we will examine the host responses and microbiome-associated profiles in calves immunized with LAV to identify a set of markers that could be used to develop an assay that can differentiate infected from vaccinated animals (DIVA). The DIVA assay will be essential and complement the SICST to allow the use of LAV, especially in states where a program for testing against bovine tuberculosis is required or needed in the future. Because of the time and budget constraints, we will develop and test the performance of the DIVA assay in a later phase of this project, but will focus our efforts on the discovery of suitable DIVA markers. Overall, we believe that our set of experimental approaches addresses the central hypothesis of this project and is sufficient to tackle the overall goal. The outcomes of this project will provide novel insights into immunopathogenesis of JD at the molecular and cellular levels.