We developed a chicken mucosa-targeting polymeric nanoparticle vaccine (~90 nm) co-delivering viral antigenCpG adjuvant using a water-in-oil-in-water double emulsion technique. The particles are biodegradablebiocompatible. This nanoparticle significantly stimulated chicken Harderian gland B cell proliferationsubsequent local IgAIgG secretion in tears. The mucosal Ig protected chickens from virus infection by lowering virus replication at the infection sitethereafter reducing tracheal epithelial ciliostasissystemic infection, relieving clinical symptoms.