Oral immunization with bacterial polysaccharide and adjuvant enhances antigen-specific pulmonary secretory antibody response and resistance to pneumonia

Abstract

Nosocomial pneumonia, often due to Pseudomonas aeruginosa, occurs frequently after haemorrhage and trauma, and contributes to the increased incidence of morbidity and mortality in this clinical setting. In order to determine if enhancement of bacterial antigen-specific secretory IgA (sIgA) titres in the lungs can increase resistance to P. aeruginosa pneumonia following haemorrhage, we investigated oral immunization strategies, using bacterial polysaccharides (levan, from Aerobacter levanicum, and P. aeruginosa polysaccharide type I) and adjuvant (cholera toxin and the B-subunit of cholera toxin), capable of increasing bacterial polysaccharide-specific pulmonary secretory antibody titres. Oral co-administration of 1000 μg levan and 10 μg cholera toxin resulted in increased titres of levan-specific sIgA in lung lavages and increased numbers of levan-specific pulmonary plasma cells, but no changes in serum anti-levan titres. Similarly, oral co-administration of 1000 μg P. aeruginosa polysaccharide and 10 μg cholera toxin produced increased anti- P. aeruginosa polysaccharide titres in lung lavages. Significant decreases in anti-levan pulmonary sIgA titres and in numbers of levan-specific pulmonary plasma cells were found when oral immunization with levan and cholera toxin was performed 4 days following haemorrhage, but not if the mice were immunized 8 h after blood loss. Although haemorrhage markedly increased the susceptibility of mice to P. aeruginosa pneumonia, significant protection from mortality could be achieved through oral immunization with 1000 μg P. aeruginosa polysacccharide and 10 μg cholera toxin 8 h after haemorrhage. These results demonstrate that haemorrhage induces marked alterations in bacterial antigen-specific pulmonary B-cell responses, which contribute to the increased susceptibility to infection in this setting. Oral immunization post haemorrhage with bacterial polysaccharides and adjuvant can improve resistance to pulmonary infection.