Induction of Trained Immunity in Broiler Chickens by Combination ofDelivery of Oligodeoxynucleotides Containing CpG Motifs and Intrapulmonary Delivery of a LiveVaccine at Hatch to Protect AgainstSepticemia Later in the Grow-Out Period.

Abstract

Bacterial infections such asand necrotic enteritis (NE) caused by(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 byandby 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 lethalsepticemia 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 theroute and intrapulmonary (IPL) route at hatch and (2) by administering CpG-ODN by theroute and IPL delivery of a CP vaccine at hatch to protect againstinfections. 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 theroute followed by delivery of a live CP vaccine by the IPL route at hatch induced trained immunity and significantly (< 0.0001) protected birds againstsepticemia at 27 days of age. Trained immunity was induced in broiler chickens only with administrations of CpG-ODN by theroute followed by the IPL route at hatch ordelivery of CpG-ODN followed by IPL delivery of a live CP vaccine at hatch. These birds were significantly (< 0.0001) protected against lethalsepticemia 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.