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Infection and Immunity, February 2009, p. 885-895, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01076-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Active and Passive Immunizations with Bordetella Colonization Factor A Protect Mice against Respiratory Challenge with Bordetella bronchiseptica{triangledown}

Neelima Sukumar,1 Cheraton F. Love,1,{dagger} Matt S. Conover,2,{dagger} Nancy D. Kock,3 Purnima Dubey,4 and Rajendar Deora1,2*

Department of Microbiology and Immunology,1 Program in Molecular Genetics,2 Department of Pathology/,4 Comparative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, North Carolina 271573

Received 29 August 2008/ Returned for modification 27 October 2008/ Accepted 26 November 2008

Bordetella colonization factor A (BcfA) is an outer membrane immunogenic protein, which is critical for efficient colonization of the murine respiratory tract. These properties of BcfA prompted us to examine its utility in inducing a protective immune response against Bordetella bronchiseptica in a mouse model of intranasal infection. Mice vaccinated with BcfA demonstrated reduced pathology in the lungs and harbored lower bacterial burdens in the respiratory tract. Immunization with BcfA led to the generation of BcfA-specific antibodies in both the sera and lungs, and passive immunization led to the reduction of B. bronchiseptica in the tracheas and lungs. These results suggest that protection after immunization with BcfA is mediated in part by antibodies against BcfA. To further investigate the mechanism of BcfA-induced immune clearance, we examined the role of neutrophils and macrophages. Our results demonstrate that neutrophils are critical for anti-BcfA antibody-mediated clearance and that opsonization with anti-BcfA serum enhances phagocytosis of B. bronchiseptica by murine macrophages. We show that immunization with BcfA results in the production of gamma interferon and subclasses of immunoglobulin G antibodies that are consistent with the induction of a Th1-type immune response. In combination, our findings suggest that the mechanism of BcfA-mediated immunity involves humoral and cellular responses. Expression of BcfA is conserved among multiple clinical isolates of B. bronchiseptica. Our results demonstrate the striking protective efficacy of BcfA-mediated immunization, thereby highlighting its utility as a potential vaccine candidate. These results also provide a model for the development of cell-free vaccines against B. bronchiseptica.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Wake Forest University Health Sciences, Medical Center Blvd., Gray 5086, Winston-Salem, NC 27157. Phone: (336) 716-1124. Fax: (336) 716-9928. E-mail: rdeora{at}wfubmc.edu

{triangledown} Published ahead of print on 8 December 2008.

Editor: J. N. Weiser

{dagger} These authors contributed equally to the work.

Infection and Immunity, February 2009, p. 885-895, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01076-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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