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Infection and Immunity, July 2007, p. 3665-3672, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01648-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Use of a Genetically Defined Double Mutant Strain of Bordetella bronchiseptica Lacking Adenylate Cyclase and Type III Secretion as a Live Vaccine{triangledown}

Paul Mann,1,2 Elizabeth Goebel,1,3 James Barbarich,1 Mylisa Pilione,1,4 Mary Kennett,1 and Eric Harvill1*

Department of Veterinary and Biomedical Sciences, Penn State University, University Park, Pennsylvania 16802,1 Graduate Program in Pathobiology, Penn State University, University Park, Pennsylvania 16802,2 Graduate Program in Immunobiology, Penn State University, University Park, Pennsylvania 16802,3 Graduate Program in Biochemistry, Microbiology and Molecular Biology, Penn State University, University Park, Pennsylvania 168024

Received 12 October 2006/ Returned for modification 30 November 2006/ Accepted 30 March 2007

While most vaccines consisting of killed bacteria induce high serum antibody titers, they do not always confer protection as effective as that induced by infection, particularly against mucosal pathogens. Bordetella bronchiseptica is a gram-negative respiratory pathogen that is endemic in many nonhuman mammalian populations and causes substantial disease in a variety of animals. At least 14 different live attenuated vaccines against this pathogen are available for use in a variety of livestock and companion animals. However, there are few published data on the makeup or efficacy of these vaccines. Here we report the use of a genetically engineered double mutant of B. bronchiseptica, which lacks adenylate cyclase and type III secretion, as a vaccine candidate. This strain is safe at high doses, even for highly immunocompromised animals, and induces immune responses that are protective against highly divergent B. bronchiseptica strains, preventing colonization in the lower respiratory tract and decreasing the bacterial burden in the upper respiratory tract. This novel B. bronchiseptica vaccine candidate induces strong local immunity while eliminating damage caused by the two predominant cytotoxic mechanisms.

* Corresponding author. Mailing address: Department of Veterinary and Biomedical Sciences, Penn State University, 115 Henning Building, University Park, PA 16802. Phone: (814) 863-8522. Fax: (814) 863-6140. E-mail: eth10{at}psu.edu

{triangledown} Published ahead of print on 23 April 2007.

Editor: D. L. Burns

Infection and Immunity, July 2007, p. 3665-3672, Vol. 75, No. 7
0019-9567/07/$08.00+0     doi:10.1128/IAI.01648-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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