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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Food Safety and Enteric Pathogens Research » Research » Research Project #431701

Research Project: Alternatives to Antibiotics: Neonatal Immunomodulation to Improve Disease Resistance in Animals

Location: Food Safety and Enteric Pathogens Research

Project Number: 5030-31320-005-12-A
Project Type: Cooperative Agreement

Start Date: Jun 1, 2020
End Date: Apr 30, 2024

Objective:
Our overall goal is to utilize innate training as an approach to enhance disease resistance in a manner that is highly relevant to both agriculture and biomedical research. In Aim 1, the efficacy of a vaccine strain of Mycobacterium bovis, BCG, as an immunomodulator will be evaluated. In Aim 2, cells from piglets and calves will be ‘trained’ in vitro and then the molecular mechanisms of innate memory will be assessed. In Aim 3, components of BCG will be tested in vitro to determine their capacity to induce innate training and their potential to be used as an alternative to BCG as a non-antibiotic immunomodulator.

Approach:
In Aim 1, the efficacy of BCG as an immunomodulator will be evaluated using two distinct infection models in two distinct species. Nursery piglets will be vaccinated with BCG, followed four weeks later by infection with either influenza virus or Escherichia coli. In parallel studies with cooperators, neonatal calves will be vaccinated with BCG, followed four weeks later by infection with either bovine respiratory syncytial virus or Pasteurella multocida. Clinical disease and host immune responses will be monitored to determine the impact of BCG treatment on disease resistance in young food animals. In Aim 2, cells from piglets and calves will be ‘trained’ in vitro and then the molecular mechanisms of innate memory will be assessed using ATAC-Seq, ChIP-seq, miRNA-seq and RNA-seq analysis. In Aim 3, components of BCG will be tested in vitro to determine their capacity to induce innate training and their potential to be used as an alternative to BCG as a non-antibiotic immunomodulator.