title: Evaluation of Borrelia burgdorferi BbHtrA Protease as a Vaccine Candidate for Lyme Borreliosis in Mice.
abstract: Borrelia burgdorferi synthesizes an HtrA protease (BbHtrA) which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B. burgdorferi and its ability to elicit an antibody response in infected hosts, we explored recombinant BbHtrA as a potential vaccine candidate in a mouse model of tick-transmitted Lyme disease. We immunized mice with two forms of BbHtrA: the proteolytically active native form and BbHtrA ablated of activity by a serine to alanine mutation at amino acid 226 (BbHtrA(S226A)). Although inoculation with either BbHtrA or BbHtrA(S226A) produced high-titer antibody responses in C3H/HeJ mice, neither antigen was successful in protecting mice from B. burgdorferi challenge. These results indicate that the search for novel vaccine candidates against Lyme borreliosis remains a challenge.
authors.affiliation: Bacterial Diseases Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, United States of America.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Ullmann
authors.affiliation: Bacterial Diseases Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, United States of America.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Russell
authors.affiliation: Bacterial Diseases Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, United States of America.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Dolan
authors.affiliation: Bacterial Diseases Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, United States of America.
authors.forename: Martin
authors.initials: M
authors.lastname: Williams
authors.affiliation: Bacterial Diseases Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, United States of America.
authors.forename: Andrias
authors.initials: A
authors.lastname: Hojgaard
authors.affiliation: Bacterial Diseases Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, United States of America.
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Weiner
authors.affiliation: Bacterial Diseases Branch, Division of Vector Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO, United States of America.
authors.forename: Barbara J B
authors.initials: BJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008193:Lyme Disease / Q000276:immunology* / Q000517:prevention & control; D022123:Lyme Disease Vaccines / Q000276:immunology*; D051379:Mice; D012697:Serine Endopeptidases / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022123:Lyme Disease Vaccines; D012697:Serine Endopeptidases