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IP10 is a predictor of successful vaccine protection against paratuberculosis infection in sheep
Hannah B Pooley1, Guneet Panag1, Karren M Plain1
1Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Camden, NSW, Australia.
Abstract:
The cell mediated immune response and ability of immune cells to migrate to the site of infection are both key aspects of protection against many pathogens. Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen and the causative agent of paratuberculosis, a chronic wasting disease of ruminants. Current commercial vaccines for paratuberculosis reduce the occurrence of clinical disease but not all animals are protected from infection. Therefore, there is a need to understand the immune responses triggered by these vaccines at the site of infection, in circulating immune cells and their relationships to vaccine-mediated protection. The magnitude and location of gene expression related to the cell mediated immune response and cellular migration were studied in the ileum of sheep. In addition, longitudinal IP10 (also known as IP10) secretion by circulating immune cells was examined in the same sheep. Animals were grouped based on vaccination status (vaccinated vs non-vaccinated) and MAP exposure (experimentally exposed vs unexposed). Vaccination of unexposed sheep increased the expression of IP10, CCL5 and COR1c. Sheep that were successfully protected by vaccination (uninfected following experimental exposure) had significantly reduced expression of IP10 in the ileum at 12 months post exposure compared to vaccine non-responders (those that became infected) and non-vaccinated infected sheep. Successfully protected sheep also had significantly increased secretion of IP10 in in vitro stimulated immune cells from whole blood compared to vaccine non responders at 4 months post exposure. Therefore, the IP10 recall response has the potential to be used as marker for infection status in vaccinated sheep and could be a biomarker for a DIVA test in sheep.
Insights
Vaccination against Mycobacterium avium subsp. paratuberculosis (MAP) in sheep influences immune responses. Protected sheep show reduced intestinal IP10 expression and increased blood immune cell IP10 secretion, indicating IP10 as a potential biomarker.
Area of Science:
- Immunology
- Veterinary Medicine
- Infectious Diseases
Background:
- Cell-mediated immunity and immune cell migration are crucial for pathogen defense.
- Mycobacterium avium subsp. paratuberculosis (MAP) causes paratuberculosis, a chronic wasting disease in ruminants.
- Current vaccines reduce clinical signs but do not guarantee complete protection, necessitating research into immune responses.
Purpose of the Study:
- To investigate immune responses at the infection site and in circulating immune cells in sheep vaccinated against MAP.
- To correlate these immune responses with vaccine-induced protection.
- To identify potential biomarkers for infection status and DIVA (differentiating infected from vaccinated animals) testing.
Main Methods:
- Studied gene expression related to cell-mediated immunity and cellular migration in the ileum of sheep.
- Measured longitudinal IP10 (interferon-gamma-induced protein 10) secretion from circulating immune cells in vaccinated and non-vaccinated, exposed and unexposed sheep.
- Grouped animals based on vaccination status and MAP exposure.
Main Results:
- Vaccination increased expression of IP10, CCL5, and COR1c in unexposed sheep.
- Successfully vaccinated and protected sheep exhibited significantly reduced ileal IP10 expression 12 months post-exposure compared to non-responders and unvaccinated infected sheep.
- Protected sheep showed significantly increased in vitro IP10 secretion from blood immune cells at 4 months post-exposure compared to vaccine non-responders.
Conclusions:
- The IP10 recall response in circulating immune cells shows potential as a marker for infection status in vaccinated sheep.
- IP10 could serve as a biomarker for developing a DIVA test in sheep.
- Understanding immune responses is key to improving vaccine efficacy and diagnostic tools for paratuberculosis.
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