Expression of B-Cell Activating Factor Enhances Protective Immunity of a Vaccine against Pseudomonas aeruginosa

Abstract

ABSTRACT 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.