title: Live Attenuated Borrelia burgdorferi Targeted Mutants in an Infectious Strain Background Protect Mice from Challenge Infection.
abstract: Borrelia burgdorferi, B. garinii, and B. afzelii are all agents of Lyme disease in different geographic locations. If left untreated, Lyme disease can cause significant and long-term morbidity, which may continue after appropriate antibiotic therapy has been administered and live bacteria are no longer detectable. The increasing incidence and geographic spread of Lyme disease are renewing interest in the vaccination of at-risk populations. We took the approach of vaccinating mice with two targeted mutant strains of B. burgdorferi that, unlike the parental strain, are avirulent in mice. Mice vaccinated with both strains were protected against a challenge with the parental strain and a heterologous B. burgdorferi strain by either needle inoculation or tick bite. In ticks, the homologous strain was eliminated but the heterologous strain was not, suggesting that the vaccines generated a response to antigens that are produced by the bacteria both early in mammalian infection and in the tick. Partial protection against B. garinii infection was also conferred. Protection was antibody mediated, and reactivity to a variety of proteins was observed. These experiments suggest that live attenuated B. burgdorferi strains may be informative regarding the identification of protective antigens produced by the bacteria and recognized by the mouse immune system in vivo Further work may illuminate new candidates that are effective and safe for the development of Lyme disease vaccines.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Hahn
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Lavinia J
authors.initials: LJ
authors.lastname: Padmore
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Ristow
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Curtis
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin, USA Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA jcoburn@mcw.edu.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Coburn
mesh_terms: D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D025065:Borrelia burgdorferi / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D004195:Disease Models, Animal; D005260:Female; D008193:Lyme Disease / Q000517:prevention & control*; D022123:Lyme Disease Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008809:Mice, Inbred C3H; D013987:Ticks / Q000382:microbiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014774:Virulence
chemical_list: D000907:Antibodies, Bacterial; D022123:Lyme Disease Vaccines; D014613:Vaccines, Attenuated