1352Progression of Lyme Disease to Later Stages is Associated with Antibody Response Towards the Membrane-Proximal Domain of the VlsE Protein of Borrelia burgdorferi

Sera collected from dogs experimentally infected withBorrelia burgdorferi by tick inoculation were analyzed for an antibody response to each of the six invariable regions (IRs; i.e., IR1 to IR6) of VlsE, the variable surface antigen of B. burgdorferi. Six synthetic peptides (C1 to C6), which reproduced the six IR sequences were used as peptide-based, enzyme-linked immunosorbent assay (ELISA) antigens. Two IRs, IR2 and IR6, were found to be immunodominant. Studies with serially collected serum samples from experimentally infected dogs revealed that the antibody response to IR6 appears earlier and is stronger than that to IR2. Thus, the IR6 sequence alone appeared to be sufficient for serodiagnosis. When C6 alone was used as antigen, the peptide-based ELISA was positive in 7 of 23 dogs (30%) as early as 3 weeks postinfection. All dogs (n = 33) became strongly positive 1 or 2 weeks later, and this response persisted for the entire study, which lasted for 69 weeks. Of 55 sera submitted by veterinarians from dogs suspected of having Lyme disease, 19 were also positive by the C6 ELISA, compared to 20 positives detected by immunoblot analysis using cultured B. burgdorferi lysates as antigen. The sensitivity of using C2 and C6 together for detecting specific antibody in both experimentally infected and clinically diagnosed dogs was not better than sensitivity with C6 alone, confirming that C6 suffices as a diagnostic probe. Moreover, the C6 ELISA yielded 100% specificity with serum samples collected from 70 healthy dogs, 14 dogs with infections other than B. burgdorferi, and 15 animals vaccinated with either outer surface protein A, whole-spirochete vaccines, or the common puppy-vaccines. Therefore, this C6 ELISA was both sensitive and specific for the serodiagnosis of canine Lyme disease and could be used with vaccinated dogs.

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Borreliacidal OspC Antibody Response of Canines with Lyme Disease Differs Significantly from That of Humans with Lyme Disease

Clinical and Vaccine Immunology ◽

10.1128/cvi.00431-06 ◽

2007 ◽

Vol 14 (5) ◽

pp. 635-637 ◽

Cited By ~ 14

Author(s):

Steven D. Lovrich ◽

Rhonda L. La Fleur ◽

Dean A. Jobe ◽

Jennifer C. Johnson ◽

Krista E. Asp ◽

...

Keyword(s):

Amino Acids ◽

Lyme Disease ◽

Borrelia Burgdorferi ◽

Antibody Response ◽

Antibody Responses ◽

Terminal Amino ◽

High Concentrations

ABSTRACT Humans reliably produce high concentrations of borreliacidal OspC antibodies specific for the seven C-terminal amino acids shortly after infection with Borrelia burgdorferi. We show that dogs also produce OspC borreliacidal antibodies but that their frequencies, intensities, and antigenicities differ significantly. The findings therefore confirm a major difference between the borreliacidal antibody responses of humans and canines with Lyme disease.

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Analysis of Antibody Response in Humans to the Type A OspC Loop 5 Domain and Assessment of the Potential Utility of the Loop 5 Epitope in Lyme Disease Vaccine Development

Clinical and Vaccine Immunology ◽

10.1128/cvi.00099-06 ◽

2006 ◽

Vol 13 (10) ◽

pp. 1162-1165 ◽

Cited By ~ 26

Author(s):

Eric L. Buckles ◽

Christopher G. Earnhart ◽

Richard T. Marconi

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Antibody Response ◽

Vaccine Development ◽

Type A ◽

Potential Utility ◽

Immunodominant Antigen ◽

Lyme Disease Vaccine ◽

Bactericidal Antibody

ABSTRACT The OspC protein of Borrelia burgdorferi is an immunodominant antigen. Here we demonstrate that the loop 5 domain of type A OspC is surface exposed, elicits bactericidal antibody in mice, and is antigenic in humans. The data suggest that loop 5 may be suitable for inclusion in a polyvalent, chimeric OspC vaccinogen.

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Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi).

Infection and Immunity ◽

10.1128/iai.57.11.3445-3451.1989 ◽

1989 ◽

Vol 57 (11) ◽

pp. 3445-3451 ◽

Cited By ~ 51

Author(s):

T G Schwan ◽

K K Kime ◽

M E Schrumpf ◽

J E Coe ◽

W J Simpson

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Antibody Response ◽

Peromyscus Leucopus

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New ultrastructural findings about Borrelia burgdorferi by cryofixation, negative staining, thin sectioning and scanning techniques

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100160467 ◽

1990 ◽

Vol 48 (3) ◽

pp. 582-583

Author(s):

S. F. Hayes ◽

M. D. Corwin ◽

T. G. Schwan ◽

D. W. Dorward ◽

W. Burgdorfer

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Structural Characterization ◽

Negative Staining ◽

Low Speed ◽

Thin Sectioning ◽

Ultrastructural Findings

Characterization of Borrelia burgdorferi strains by means of negative staining EM has become an integral part of many studies related to the biology of the Lyme disease organism. However, relying solely upon negative staining to compare new isolates with prototype B31 or other borreliae is often unsatisfactory. To obtain more satisfactory results, we have relied upon a correlative approach encompassing a variety EM techniques, i.e., scanning for topographical features and cryotomy, negative staining and thin sectioning to provide a more complete structural characterization of B. burgdorferi.For characterization, isolates of B. burgdorferi were cultured in BSK II media from which they were removed by low speed centrifugation. The sedimented borrelia were carefully resuspended in stabilizing buffer so as to preserve their features for scanning and negative staining. Alternatively, others were prepared for conventional thin sectioning and for cryotomy using modified procedures. For thin sectioning, the fixative described by Ito, et al.

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Computational Studies on the Truncation of N-terminal Fragment of OspA Antigen of Borrelia burgdorferi: Towards Designing a Second- Generation Vaccine Against Lyme Disease

Current Proteomics ◽

10.2174/157016461104150121114715 ◽

2015 ◽

Vol 11 (4) ◽

pp. 264-280

Author(s):

Dieudonne Mutangana ◽

Ramesh K. V. ◽

Maithri S. K.

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Second Generation ◽

Computational Studies ◽

Terminal Fragment ◽

Generation Vaccine

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Surveillance of Ticks and Tick-Borne Pathogens in Suburban Natural Habitats of Central Maryland

Journal of Medical Entomology ◽

10.1093/jme/tjaa291 ◽

2021 ◽

Author(s):

Matthew T Milholland ◽

Lars Eisen ◽

Robyn M Nadolny ◽

Andrias Hojgaard ◽

Erika T Machtinger ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Spotted Fever ◽

Babesia Microti ◽

Borrelia Burgdorferi Sensu Lato ◽

Spotted Fever Group ◽

Borrelia Miyamotoi ◽

Natural Habitats ◽

Questing Ticks ◽

Tick Vectors

Abstract Lyme and other tick-borne diseases are increasing in the eastern United States and there is a lack of research on integrated strategies to control tick vectors. Here we present results of a study on tick-borne pathogens detected from tick vectors and rodent reservoirs from an ongoing 5-yr tick suppression study in the Lyme disease-endemic state of Maryland, where human-biting tick species, including Ixodes scapularis Say (Acari: Ixodidae) (the primary vector of Lyme disease spirochetes), are abundant. During the 2017 tick season, we collected 207 questing ticks and 602 ticks recovered from 327 mice (Peromyscus spp. (Rodentia: Cricetidae)), together with blood and ear tissue from the mice, at seven suburban parks in Howard County. Ticks were selectively tested for the presence of the causative agents of Lyme disease (Borrelia burgdorferi sensu lato [s.l.]), anaplasmosis (Anaplasma phagocytophilum), babesiosis (Babesia microti), ehrlichiosis (Ehrlichia ewingii, Ehrlichia chaffeensis, and ‘Panola Mountain’ Ehrlichia) and spotted fever group rickettsiosis (Rickettsia spp.). Peromyscus ear tissue and blood samples were tested for Bo. burgdorferi sensu stricto (s.s), A. phagocytophilum, Ba. microti, and Borrelia miyamotoi. We found 13.6% (15/110) of questing I. scapularis nymphs to be Bo. burgdorferi s.l. positive and 1.8% (2/110) were A. phagocytophilum positive among all sites. Borrelia burgdorferi s.s. was found in 71.1% (54/76) of I. scapularis nymphs removed from mice and 58.8% (194/330) of captured mice. Results from study on tick abundance and pathogen infection status in questing ticks, rodent reservoirs, and ticks feeding on Peromyscus spp. will aid efficacy evaluation of the integrated tick management measures being implemented.

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Arthritis and Diagnostics in Lyme Disease

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6010018 ◽

2021 ◽

Vol 6 (1) ◽

pp. 18

Author(s):

Javier A. Quintero ◽

Raluchukwu Attah ◽

Reena Khianey ◽

Eugenio Capitle ◽

Steven E. Schutzer

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Diagnostic Tests ◽

Laboratory Tests ◽

Diagnostic Methods ◽

Lyme Arthritis ◽

Differential Diagnoses ◽

Antibody Testing ◽

Active Infection ◽

Indirect Measure

The diagnosis of Lyme disease, caused by Borrelia burgdorferi, is clinical but frequently supported by laboratory tests. Lyme arthritis is now less frequently seen than at the time of its discovery. However, it still occurs, and it is important to recognize this, the differential diagnoses, and how laboratory tests can be useful and their limitations. The most frequently used diagnostic tests are antibody based. However, antibody testing still suffers from many drawbacks and is only an indirect measure of exposure. In contrast, evolving direct diagnostic methods can indicate active infection.

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Populations of Human T Lymphocytes That Traverse the Vascular Endothelium Stimulated by Borrelia burgdorferi Are Enriched with Cells That Secrete Gamma Interferon

Infection and Immunity ◽

10.1128/iai.72.3.1530-1536.2004 ◽

2004 ◽

Vol 72 (3) ◽

pp. 1530-1536 ◽

Cited By ~ 11

Author(s):

Edna I. Gergel ◽

Martha B. Furie

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Lyme Disease ◽

Borrelia Burgdorferi ◽

Vascular Endothelium ◽

Human Peripheral Blood ◽

Gamma Interferon ◽

Interleukin 4 ◽

Ifn Γ

ABSTRACT Some diseases are characterized by prevalence in the affected tissues of type 1 T lymphocytes, which secrete gamma interferon (IFN-γ) and other proinflammatory cytokines. For example, type 1 T cells predominate in the lesions of patients with Lyme disease, which is caused by the bacterium Borrelia burgdorferi. We used an in vitro model of the blood vessel wall to test the premise that the vascular endothelium actively recruits circulating type 1 T cells to such lesions. When T lymphocytes isolated from human peripheral blood were examined, the populations that traversed monolayers of resting human umbilical vein endothelial cells (HUVEC) or HUVEC stimulated by interleukin-1β or B. burgdorferi were markedly enriched for T cells that produced IFN-γ compared to the initially added population of T cells. No enrichment was seen for cells that produced interleukin-4, a marker for type 2 T lymphocytes. Very late antigen-4 and CD11/CD18 integrins mediated passage of the T cells across both resting and stimulated HUVEC, and the endothelium-derived chemokine CCL2 (monocyte chemoattractant protein 1) was responsible for the enhanced migration of T cells across stimulated HUVEC. These results suggest that the vascular endothelium may contribute to the selective accumulation of type 1 T cells in certain pathological lesions, including those of Lyme disease.

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C-Terminal Invariable Domain of VlsE Is Immunodominant but Its Antigenicity Is Scarcely Conserved among Strains of Lyme Disease Spirochetes

Infection and Immunity ◽

10.1128/iai.69.5.3224-3231.2001 ◽

2001 ◽

Vol 69 (5) ◽

pp. 3224-3231 ◽

Cited By ~ 17

Author(s):

Fang Ting Liang ◽

Lisa C. Bowers ◽

Mario T. Philipp

Keyword(s):

Lyme Disease ◽

Antibody Response ◽

Human Serum ◽

Synthetic Peptide ◽

Species Complex ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Variable Surface ◽

Entire Sequence ◽

Carboxyl Terminal

ABSTRACT VlsE, the variable surface antigen of Borrelia burgdorferi, contains two invariable domains located at the amino and carboxyl terminal ends, respectively, and a central variable domain. In this study, both immunogenicity and antigenic conservation of the C-terminal invariable domain were assessed. Mouse antiserum to a 51-mer synthetic peptide (Ct) which reproduced the entire sequence of the C-terminal invariable domain of VlsE from B. burgdorferi strain B31 was reacted on immunoblots with whole-cell lysates extracted from spirochetes of 12 strains from the B. burgdorferi sensu lato species complex. The antiserum recognized only VlsE from strain B31, indicating that epitopes of this domain differed among these strains. When Ct was used as enzyme-linked immunosorbent assay (ELISA) antigen, all of the seven monkeys and six mice that were infected with B31 spirochetes produced a strong antibody response to this peptide, indicating that the C-terminal invariable domain is immunodominant. None of 12 monkeys and only 11 of 26 mice that were infected with strains other than B31 produced a detectable anti-Ct response, indicating a limited antigenic conservation of this domain among these strains. Twenty-six of 33 dogs that were experimentally infected by tick inoculation were positive by the Ct ELISA, while only 5 of 18 serum samples from dogs clinically diagnosed with Lyme disease contained detectable anti-Ct antibody. Fifty-seven of 64 serum specimens that were collected from American patients with Lyme disease were positive by the Ct ELISA, while only 12 of 21 European samples contained detectable anti-Ct antibody. In contrast, antibody to the more conserved invariable region IR6 of VlsE was present in all of these dog and human serum samples.

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