Location: Infectious Bacterial Diseases Research
Project Number: 5030-32000-235-000-D
Project Type: In-House Appropriated
Start Date: Oct 6, 2021
End Date: Oct 5, 2026
Objective:
Objective 1: Through genomic–scale approaches, identify MAP antigens for improved detection of Johne’s disease in cattle, including early stage infection. Building on this approach, identify and test selected antigens that could be used as vaccine candidates.
Sub-objective 1.A: Design a synthetic antigen comprising strong epitopes from MAP antigens detected early in MAP infection of cattle.
Sub-objective 1.B: Use genomic approaches to discover new vaccine and diagnostic targets in MAP and improve on current diagnostic tests.
Sub-objective 1.C: Establish a CRISPR/Cas9 gene editing system in MAP for fast and targeted gene disruption to create live attenuated vaccine strains.
Objective 2: Characterize the host’s innate-immune response to onset of MAP infection in order to identify and develop novel intervention strategies to control infection with MAP.
Sub-objective 2.A: Characterize patterns of innate immune responses to natural infection in cattle in asymptomatic and clinical stages.
Sub-objective 2.B: Characterize the presence of innate immune cells in tissues at the site of infection from naturally infected cattle.
Approach:
First identified over a century ago, Johne’s disease (a.k.a. Paratuberculosis) has long been recognized as a serious economic and animal health problem throughout the world in domesticated ruminants such as dairy and beef cattle, sheep, and goats. Paratuberculosis results in more than $200 million in annual losses to the U.S. dairy industry each year with additional losses incurred by the other species. The agent that causes this disease is the slow growing bacterium Mycobacterium avium subspecies paratuberculosis (MAP). A growing recognition of MAP infection in wildlife species is also of considerable concern, as is the recent implication of the presence of MAP in retail milk sources that may make this pathogen a risk from a milk quality and food safety standpoint. The overall goal of the work described in this project is to reduce the impact of Johne’s disease on the livestock producer and their corresponding industries. This goal is best accomplished by understanding the bovine immune response and what role specific immune cells play in order to inform next generation vaccine development and to identify antigens and assay platforms with the ability to detect the disease earlier, before transmission and disease spread occurs. With this goal and approaches in mind, we propose two primary objectives: (1) Through genomic–scale approaches, identify MAP antigens for improved detection of Johne’s disease in cattle, including early stage infection. Building on this approach, identify and test selected antigens that could be used as vaccine candidates; (2) Characterize the host’s innate-immune response to onset of MAP infection in order to identify and develop novel intervention strategies to control infection with MAP. This research will not only expand the basic knowledge of the disease, but it will lead to countermeasures to combat the disease, providing significant economic benefits to livestock producers.
