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


OBJECTIVE
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.


METHODS
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.
Department of Pneumology, University of Freiburg, Freiburg, Germany.
Stephan
S
Sorichter
Ulrich
U
Baumann
Astrid
A
Baumgart
Stephan
S
Walterspacher
Bernd-Ulrich
BU
von Specht
D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000009:adverse effects / Q000379:methods*; D008171:Lung Diseases / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology; D011552:Pseudomonas Infections / Q000276:immunology*; D054406:Pseudomonas Vaccines / Q000009:adverse effects / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*
D000914:Antibodies, Viral; D054406:Pseudomonas Vaccines