Mucosal and systemic immunizations with killed Pseudomonas aeruginosa protect against acute respiratory infection in rats

Abstract

The aim of this study was to determine the efficacies of prior mucosal (oral, intra-Peyer's patch, or intratracheal) and systemic (subcutaneous) immunizations with killed Pseudomonas aeruginosa in clearance of an acute P. aeruginosa respiratory infection in rats. Rats were immunized with paraformaldehyde-killed P. aeruginosa at various doses, and 2 weeks later, the rats were challenged with a log10 dose of 8.7 live bacteria. This dose was fatal for unimmunized rats, with death occurring approximately 12 h after challenge. The numbers of surviving bacteria in the airways and lung tissue were determined by analyses of bronchoalveolar lavage fluid (BAL) and lung homogenate samples, respectively. Enhanced bacterial clearance was associated with survival of intra-Peyer's patch-immunized rats. Determination of bacterial clearance in BAL 4 h after challenge demonstrated that the use of all immunization routes led to significant clearance compared with the bacterial levels in unimmunized controls (the order of effectiveness was intra-Peyer's patch > oral-intratracheal > intratracheal > subcutaneous > oral). Bacterial clearance in the lung homogenate was also significantly greater for all immunization routes than in the unimmunized controls (the order of effectiveness was intra-Peyer's patch > subcutaneous > oral-intratracheal > oral = intratracheal). Prior oral immunization with killed P. aeruginosa also induced enhanced bacterial clearance of heterologous strains of P. aeruginosa, Haemophilus influenzae, and to a lesser extent, Klebsiella pneumoniae. Because of the ease of antigen delivery, oral immunization with killed P. aeruginosa may be an important route of immunization for induction of enhanced bacterial clearance of subsequent acute respiratory infection with P. aeruginosa and other gram-negative bacteria.