Evaluation of Borrelia burgdorferi BbHtrA Protease as a Vaccine Candidate for Lyme Borreliosis in Mice

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...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0128868-e0128868
Main Authors: Ullmann, Amy J, Russell, Theresa M, Dolan, Marc C, Williams, Martin, Hojgaard, Andrias, Weiner, Zachary P, Johnson, Barbara J B
Format: Article
Language:English
Subjects:
Aggrecan
Alanine
Aluminum
Amino acids
Animals
Antibiotics
Antibodies, Bacterial - blood
Antibodies, Bacterial - immunology
Antibody response
Antigens
Arachnids
Bacterial Proteins - immunology
Borrelia
Borrelia burgdorferi
Borrelia burgdorferi - immunology
Borreliosis
Cell cycle
Chlamydia
Chlamydia muridarum
Disease control
Disease Models, Animal
Disease prevention
Female
Fibronectin
Haemophilus influenzae
Immunization
Immunoglobulin G - blood
Immunoglobulin G - immunology
Immunology
Infections
Inoculation
Laboratory animals
Lyme disease
Lyme Disease - immunology
Lyme Disease - prevention & control
Lyme Disease Vaccines - immunology
Medical laboratories
Mice
Mutation
Orientia tsutsugamushi
Parasitic diseases
Protease
Proteinase
Proteins
Proteoglycans
Rabbits
Serine
Serine Endopeptidases - immunology
Skin
Spirochetes
Vaccines
Vector-borne diseases
Vectors (Biology)
Vertebrates
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0128868