Assessment of pulmonary antibodies with induced sputum and bronchoalveolar lavage induced by nasal vaccination against Pseudomonas aeruginosa: a clinical phase I/II study.
BACKGROUND
Vaccination against Pseudomonas aeruginosa is a desirable albeit challenging strategy for prevention of airway infection in patients with cystic fibrosis. We assessed the immunogenicity of a nasal vaccine based on the outer membrane proteins F and I from Pseudomonas aeruginosa in the lower airways in a phase I/II clinical trial.


METHODS
N = 12 healthy volunteers received 2 nasal vaccinations with an OprF-OprI gel as a primary and a systemic (n = 6) or a nasal booster vaccination (n = 6). Antibodies were assessed in induced sputum (IS), bronchoalveolar lavage (BAL), and in serum.


RESULTS
OprF-OprI-specific IgG and IgA antibodies were found in both BAL and IS at comparable rates, but differed in the predominant isotype. IgA antibodies in IS did not correlate to the respective serum levels. Pulmonary antibodies were detectable in all vaccinees even 1 year after the vaccination. The systemic booster group had higher IgG levels in serum. However, the nasal booster group had the better long-term response with bronchial antibodies of both isotypes.


CONCLUSIONS
The nasal OprF-OprI-vaccine induces a lasting antibody response at both, systemic and airway mucosal site. IS is a feasible method to non-invasively assess bronchial antibodies. A further optimization of the vaccination schedule is warranted.
Department of Paediatric Pulmonology and Neonatalogy, Hanover Medical School, Hannover, Germany. baumann.ulrich@mh-hannover.de
Ulrich
U
Baumann
Kerstin
K
Göcke
Britta
B
Gewecke
Joachim
J
Freihorst
Bernd Ulrich
BU
von Specht
D000281:Administration, Intranasal; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D005240:Feasibility Studies; D005782:Gels; D006801:Humans; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007273:Injections, Intramuscular; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012016:Reference Values; D020545:Respiratory Mucosa / Q000276:immunology; D013183:Sputum / Q000276:immunology*; D013997:Time Factors; D014611:Vaccination / Q000379:methods*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D005782:Gels; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008074:Lipoproteins; D011993:Recombinant Fusion Proteins; C060507:outer membrane lipoprotein I, Bacteria