Milk-derived antimicrobial peptides to protect against Neonatal Diarrheal Disease: An alternative to antibiotics

Neonatal Diarrheal Disease is responsible for significant economic losses to the livestock industries in Canada and around the world. Microbes responsible are diverse and include Escherichia coli, Salmonella, Rotavirus, Coronavirus and Cryptosporidia. While the use of antibiotics as a treatment for bacterial infections and as a prophylactic additive in feed has dramatically improved cattle production in recent decades, the increasing pressure to reduce or eliminate use of antibiotics in animals has caused the livestock industry to seek appropriate alternatives. Antimicrobial/Host Defense Peptides are natural compounds present on skin and in secretions in plants and animals that are microbicidal for bacteria, viruses, and parasites and they stimulate the immune system to combat infectious diseases. Our objective is to establish orally-obtained Host Defense Peptides (HDPs) as an alternative to antibiotics to protect against Neonatal Diarrheal Disease in calves. We devised a method to allow the cow udder to act as a factory to produce HDPs so that suckling calves will receive a continuous oral dose of HDPs over several weeks to protect them against neonatal diarrhea. We will use Adenovirus to deliver a gene coding for several HDPs in-frame into mammary epithelial cells. The epithelial cells will secrete the HDP protein into milk to be consumed by the suckling calves and trypsin in the calf gut will release the HDPs through cleavage. Thus, the novelty of this research lies not only in the proposed alternative to antibiotics to protect neonates against disease, but in the method by which we introduce the peptides to the suckling offspring.