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Infection and Immunity, July 2009, p. 3044-3055, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00927-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Christine Tertilt,1,3 Ju Joh,1 Anja Krause,1 Paigee Chou,2 Kristin Schneeweiss,3 Ronald G. Crystal,1 and Stefan Worgall1,2*

Department of Genetic Medicine,1 Department of Pediatrics, Weill Medical College of Cornell University, New York, New York,2 Department of Immunology, Johannes Gutenberg-University, Mainz, Germany3

Received 25 July 2008/ Returned for modification 24 October 2008/ Accepted 10 March 2009

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.

* Corresponding author. Mailing address: Department of Pediatrics, Weill Medical College of Cornell University, 515 East 71st Street, S-614, New York, NY 10021. Phone: (212) 746-4875. Fax: (212) 746-8261. E-mail: geneticmedicine{at}med.cornell.edu

{triangledown} Published ahead of print on 13 April 2009.

Editor: R. P. Morrison

Infection and Immunity, July 2009, p. 3044-3055, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00927-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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