Use of a genetically defined double mutant strain of Bordetella bronchiseptica lacking adenylate cyclase and type III secretion as a live vaccine.
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.
Mann
Paul
P
Department of Veterinary and Biomedical Sciences, Penn State University, 115 Henning Building, University Park, PA 16802, USA.
Goebel
Elizabeth
E
Barbarich
James
J
Pilione
Mylisa
M
Kennett
Mary
M
Harvill
Eric
E
D000262:Adenylyl Cyclases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D001885:Bordetella Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D016950:Bordetella bronchiseptica / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D042483:Bordetella parapertussis / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology; D005818:Genetic Engineering / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009154:Mutation; D012137:Respiratory System / Q000382:microbiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014917:Whooping Cough / Q000276:immunology / Q000517:prevention & control
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D000262:Adenylyl Cyclases