Immune responses in the airways by nasal vaccination with systemic boosting against Pseudomonas aeruginosa in chronic lung disease

Abstract

Rationale Pneumonia caused by Pseudomonas ( P.) aeruginosa is a leading cause of morbidity and mortality in patients with chronic lung diseases. Systemic vaccination in patients with cystic fibrosis has been only successful in part. Mucosal vaccination could lead to enhanced airway immunogenicity. Pathogen specific secretory IgA antibodies could prevent bacterial invasion into the lung mucosa. Objectives A phase 1–2 mucosal vaccination trial with an intranasal P. aeruginosa vaccine was performed. Methods 12 patients with chronic lung diseases (8 COPD, 2 cystic fibrosis, 1 bronchiectasis, 1 histiocytosis X) were vaccinated three times intranasally followed by a systemic booster vaccination with a recombinant hybrid protein encompassing the main protective epitopes of two outer membrane proteins of P. aeruginosa. Mucosal and systemic antibody responses were measured after boosting and after a half-year follow-up compared to a representative control cohort. Measurements Specific IgG and IgA antibodies in the patient's sera, saliva and sputum were determined by enzyme-linked immunosorbent assay (ELISA) and IgG subclass distributions were defined with monoclonal mouse antibodies. Results Both forms of vaccination were well tolerated. Significant elevated IgA and IgG antibodies could be measured in sputum, saliva and in the sera of 11/12 patients. Conclusions Mucosal vaccination followed by systemic boost with an outer membrane protein vaccine against P. aeruginosa leads to airway immunogenicity against the pathogen. Further clinical trials should elucidate the protective efficacy of this vaccination method.