Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa: a clinical trial of immunogenicity in lower airways of human volunteers.
Vaccination against Pseudomonas aeruginosa is a desirable, yet challenging strategy for prevention of airway infection in patients with cystic fibrosis. We compared the formation of antibodies in lower airways induced by systemic and mucosal vaccination strategies. We immunised 48 volunteers in six vaccination groups with either a systemic, a nasal, or four newly constructed oral live vaccines based on attenuated live Salmonella (strains CVD908 and Ty21a), followed by a systemic booster vaccination. All vaccines were based on a recombinant fusion protein of the highly conserved P. aeruginosa outer membrane proteins OprF and OprI as antigen. While systemic and mucosal vaccines induced a comparable rise of serum antibody titers, a significant rise of IgA and IgG antibodies in the lower airways was noted only after nasal and oral vaccinations. We conclude that nasal and oral OprF-OprI vaccines are promising candidates for development of antipseudomonal immunisation through inducing a specific antibody response in the lung.
Bumann
Dirk
D
Junior Research Group Mucosal Immunology, Department of Immunology, Hanover Medical School, Hannover, Germany.
Behre
Christoph
C
Behre
Katharina
K
Herz
Steffen
S
Gewecke
Britta
B
Gessner
J Engelbert
JE
von Specht
Bernd Ulrich
BU
Baumann
Ulrich
U
D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D006805:Human Experimentation; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000517:prevention & control*; D054406:Pseudomonas Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012137:Respiratory System / Q000276:immunology; D012475:Salmonella / Q000235:genetics; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D054406:Pseudomonas Vaccines; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated