Expression of B-cell activating factor enhances protective immunity of a vaccine against Pseudomonas aeruginosa.
B-cell activating factor (BAFF), a member of the TNF family, is a potent cytokine with stimulatory effects on B and T cells. To evaluate the potential of transient overexpression of BAFF to enhance vaccine immunogenicity, a replication-deficient adenovirus expressing full-length murine BAFF (AdBAFF) was tested in a mouse vaccine model against Pseudomonas aeruginosa. When coadministered with heat-killed P. aeruginosa, AdBAFF mediated a significant increase in anti-P. aeruginosa-specific serum and lung mucosal antibodies and resulted in improved protection against a lethal respiratory challenge with P. aeruginosa. This effect was independent of the site of administration of AdBAFF and was observed both when AdBAFF was given simultaneously with heat-killed P. aeruginosa as well as when AdBAFF was administered 4 weeks after immunization with heat-killed P. aeruginosa. These data demonstrate that a temporal increase in systemic BAFF levels is able to augment a P. aeruginosa-specific immune response upon immunization with heat-killed P. aeruginosa, suggesting that the immune-stimulatory effects of BAFF may be exploited as a molecular adjuvant for genetic vaccines.
Department of Pediatrics, Weill Medical College of Cornell University, New York, New York 10021, USA.
Christine
C
Tertilt
Ju
J
Joh
Anja
A
Krause
Paigee
P
Chou
Kristin
K
Schneeweiss
Ronald G
RG
Crystal
Stefan
S
Worgall
D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D053264:B-Cell Activating Factor / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D005822:Genetic Vectors; D018928:Immunity, Mucosal; D051379:Mice; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000276:immunology; D054406:Pseudomonas Vaccines / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D053264:B-Cell Activating Factor; D054406:Pseudomonas Vaccines; D015164:Vaccines, Inactivated