Protection of Broiler Chickens Against Necrotic Enteritis by Intrapulmonary Delivery of a Live Clostridium perfringens Vaccine Exploiting the Gut-Lung–Axis Concept

<i>Clostridium perfringens</i> (CP)-induced necrotic enteritis (NE) is an economically important disease in the broiler chicken industry. The incidence of NE is common in 3-to-6-wk-old broiler chickens, once maternal antibodies start declining. Developing an effective vaccination strategy against NE, preferably delivering a single dose of vaccine at hatch to protect broiler chickens against NE without a booster vaccine, is an enormous challenge. The objective of this study was to induce mucosal immunity in the intestines against NE by intrapulmonary (IPL) delivery of a live CP vaccine at hatch, exploiting the gut-lung-axis (GLA) concept by vaccine delivery following <i>in ovo</i> administration of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODN) to induce immune cell maturation in the lungs. Experiments were conducted to explore the dose of CP and immune protection against heterologous CP challenge, and to study the efficacy of IPL delivery of a CP vaccine without a booster. Additional studies were conducted to measure serum immunoglobulin (Ig)Y, mucosal IgA, and histopathology of lungs following vaccination. Delivery of a live CP vaccine by the IPL route, with or without <i>in ovo</i> CpG-ODN, provided significant protection against NE (<i>P</i> < 0.0001). Systemic IgY and mucosal IgA against CP were correlated with protection against NE. There was no necrosis or inflammation in the pulmonary parenchyma. There was a low number of CP isolated from the lungs following live CP delivery by the IPL route. A significant influx of (<i>P</i> < 0.001) of CD8+ T cells and macrophages were noted in the lungs 2 days following live CP delivery by the IPL route. IPL delivery of a live CP vaccine, rather than inactivated CP, provided better protection. This study demonstrated the utility in exploiting the GLA concept in vaccine delivery in broiler chickens.