Induction of Trained Immunity in Broiler Chickens by Combination of in Ovo Delivery of Oligodeoxynucleotides Containing CpG Motifs and Intrapulmonary Delivery of a Live Clostridium perfringens Vaccine at Hatch to Protect Against Escherichia coli Septicemia Later in the Grow-Out Period.

Abstract

Bacterial infections such as Escherichia coli and necrotic enteritis (NE) caused by Clostridium perfringens (CP) are responsible for significant economic losses in the broiler chicken industry. Our previous studies have involved trying to develop alternatives to antimicrobials and immunoprotective agents to such pathogens. Previously, we demonstrated that delivery of a single dose of oligodeoxynucleotides containing unmethylated cytosine-phosphodiester-guanine motifs (CpG-ODN) can promote antimicrobial immunity against yolk sac infections caused by E. coli and Salmonella by enriching immune compartments and activating immune cells. Recently, we have demonstrated delivery of CpG-ODN twice by the intramuscular (IM) route in neonatal broiler chickens at Days 1 and 4 of age to induce trained immunity and protect against lethal E. coli septicemia later in the grow-out period. The objectives of this study were to explore the ability of CpG-ODN to induce trained immunity in broiler chickens (1) by administering CpG-ODN by the in ovo route and intrapulmonary (IPL) route at hatch and (2) by administering CpG-ODN by the in ovo route and IPL delivery of a CP vaccine at hatch to protect against E. coli infections. Intramuscular (IM) delivery of CpG-ODN twice at Days 1 and 4 of age in neonatal broiler chickens induced trained immunity to protect against NE. Induction of trained immunity in broiler chickens led to a switch in cellular energy metabolism of immune cells from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) following two administrations of CpG-ODN. We have also demonstrated that delivery of CpG-ODN by the in ovo route followed by delivery of a live CP vaccine by the IPL route at hatch induced trained immunity and significantly (P < 0.0001) protected birds against E. coli septicemia at 27 days of age. Trained immunity was induced in broiler chickens only with administrations of CpG-ODN by the in ovo route followed by the IPL route at hatch or in ovo delivery of CpG-ODN followed by IPL delivery of a live CP vaccine at hatch. These birds were significantly (P < 0.0001) protected against lethal E. coli septicemia and NE later in the production cycle, demonstrating the utility of CpG-ODN for induction of trained immunity and broad-spectrum protection of broiler chickens against common lethal bacterial infections.