scholarly journals Persistent Anti- Borrelia IgM Antibodies without Lyme Borreliosis in the Clinical and Immunological Context

2021 ◽  
Vol 9 (3) ◽  
Author(s):  
Mateusz Markowicz ◽  
Michael Reiter ◽  
Jutta Gamper ◽  
Gerold Stanek ◽  
Hannes Stockinger
Keyword(s):  
Borrelia Burgdorferi ◽  
Lyme Borreliosis ◽  
Outer Surface ◽  
Early Phase ◽  
Protein C ◽  
Surface Protein ◽  
Content Type ◽  
Igm Antibodies ◽  
Outer Surface Protein

The reactivity of human IgM with the outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is frequently used to detect Borrelia specific IgM in commercial immunoassays, and such antibodies usually occur in the early phase of the infection. We identified a group of individuals with persistent Borrelia IgM without symptoms of Lyme borreliosis.

scholarly journals Enhanced Protective Immunogenicity of Homodimeric Borrelia burgdorferi Outer Surface Protein C

2016 ◽  
Vol 24 (1) ◽  
Author(s):  
Diane G. Edmondson ◽  
Sabitha Prabhakaran ◽  
Steven J. Norris ◽  
Amy J. Ullmann ◽  
Joe Piesman ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Protein C ◽  
Dose Range ◽  
Surface Protein ◽  
The United States ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Content Type ◽  
Outer Surface Protein ◽  
Dimeric Form

ABSTRACTLyme borreliosis is caused by tick-transmitted spirochetes of theBorrelia burgdorferi sensu latogroup and is the most common vector-borne disease in the United States and Europe. Outer surface protein C (OspC) is a 23-kDa outer surface lipoprotein expressed during spirochete transmission from the tick to the vertebrate host. In a previous study, we found that immunization with a recombinant disulfide-bridged dimeric form of OspC (D-OspC) stimulates increased antibody responses relative to immunization with commonly employed monomeric OspC. Here, we report that mice immunized with dimeric OspC proteins also exhibited enhanced protection against infection with the cognateB. burgdorferistrain. Mice were protected by four immunizations containing as little as 100 ng of dimeric OspC, suggesting that this form of the protein can induce protective immunity within a dose range reasonable for a human or veterinary vaccine. In contrast, monomeric OspC was only partially protective at much higher doses. IgG subclass analysis revealed that D-OspC-immunized animals mainly possessed anti-OspC-IgG1. In contrast, infected animals develop anti-OspC restricted to the IgG3 isotype. A subset of antibodies generated by dimeric OspC immunization did not recognize the monomeric variant, indicating that unique epitopes exist on the dimeric form. Moreover, monoclonal antibodies that recognized only dimeric OspC protected mice fromB. burgdorferichallenge, whereas another monoclonal that recognized both immunogens was not protective. These studies suggest that this dimeric OspC presents distinctive epitopes that generate antibodies protective againstB. burgdorferiinfection and could be a useful vaccine component.

A new specific serodiagnosis system for Lyme disease: use of synthetic peptides derived from outer surface protein C of Borrelia burgdorferi

1997 ◽  
Vol 9 (1) ◽  
pp. 21-25 ◽  
Author(s):  
M. Ikushima ◽  
S. Kawahashi ◽  
Y. Ohzeki ◽  
Y. Okuyama ◽  
E. Isogai ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Synthetic Peptides ◽  
Protein C ◽  
Surface Protein ◽  
Outer Surface Protein

scholarly journals Constitutive Expression of Outer Surface Protein C Diminishes the Ability of Borrelia burgdorferi To Evade Specific Humoral Immunity

2006 ◽  
Vol 74 (9) ◽  
pp. 5177-5184 ◽  
Author(s):  
Qilong Xu ◽  
Sunita V. Seemanapalli ◽  
Kristy McShan ◽  
Fang Ting Liang
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Protein C ◽  
Severe Combined Immunodeficiency ◽  
Constitutive Expression ◽  
Surface Protein ◽  
Start Codon ◽  
Chronic Infections ◽  
Translational Initiation ◽  
Outer Surface Protein

ABSTRACT The Lyme disease spirochete Borrelia burgdorferi reduces the expression of outer surface protein C (OspC) in response to the development of an anti-OspC humoral response, leading to the hypothesis that the ability to repress OspC expression is critical for the pathogen to proceed to chronic infection. B. burgdorferi was genetically modified to constitutively express OspC by introducing an extra ospC copy fused with the borrelial flagellar gene (flaB) promoter. Such a genetic modification did not reduce infectivity or pathogenicity in severe combined immunodeficiency mice but resulted in clearance of infection by passively transferred OspC antibody. Spirochetes with constitutive ospC expression were unable to establish chronic infections in immunocompetent mice unless they had undergone very destructive mutations in the introduced ospC copy. Two escape mutants were identified; one had all 7 bp deleted between the putative ribosome-binding site and the start codon, ATG, causing a failure in translational initiation, and the other mutant had an insertion of 2 bp between nucleotides 315 and 316, resulting in a nonsense mutation at codon 108. Thus, the ability of B. burgdorferi to repress ospC expression during mammalian infection allows the pathogen to avoid clearance and to preserve the integrity of the important gene for subsequent utilization during its enzootic life cycle.

scholarly journals Outer Surface Protein C Is a Dissemination-Facilitating Factor of Borrelia burgdorferi during Mammalian Infection

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15830 ◽  
Author(s):  
Sunita V. Seemanapalli ◽  
Qilong Xu ◽  
Kristy McShan ◽  
Fang Ting Liang
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Protein C ◽  
Surface Protein ◽  
Outer Surface Protein ◽  
Mammalian Infection

scholarly journals Identification of B-cell epitopes of Borrelia burgdorferi outer surface protein C by screening a phage-displayed gene fragment library

2016 ◽  
Vol 60 (10) ◽  
pp. 669-677 ◽  
Author(s):  
Lucia Pulzova ◽  
Zuzana Flachbartova ◽  
Elena Bencurova ◽  
Lenka Potocnakova ◽  
Lubos Comor ◽  
...  
Keyword(s):  
Borrelia Burgdorferi ◽  
B Cell ◽  
Outer Surface ◽  
Protein C ◽  
Surface Protein ◽  
Gene Fragment ◽  
B Cell Epitopes ◽  
Outer Surface Protein ◽  
Fragment Library

scholarly journals Conformational Nature of the Borrelia burgdorferi B31 Outer Surface Protein C Protective Epitope

1999 ◽  
Vol 67 (10) ◽  
pp. 5463-5469 ◽  
Author(s):  
Robert D. Gilmore ◽  
M. Lamine Mbow
Keyword(s):  
Borrelia Burgdorferi ◽  
Outer Surface ◽  
Protein C ◽  
Surface Protein ◽  
Active Immunization ◽  
Laboratory Animals ◽  
Transmitted Infection ◽  
Infectious Dose ◽  
Outer Surface Protein ◽  
Protective Epitope

ABSTRACT Active immunization with Escherichia coli-expressed recombinant outer surface protein C (OspC) of Borrelia burgdorferi has been demonstrated to confer protection against a tick-transmitted infection on laboratory animals. A previous study in this laboratory showed that OspC antibody raised against a denatured immunogen isolated from B. burgdorferi cells failed to provide protective immunity. Therefore, to determine whether the protective epitope of the recombinant antigen was sensitive to denaturation, recombinant OspC preparations were subjected to heat and chemical treatments prior to animal immunization. Following seroconversion to OspC, the animals were challenged with an infectious dose of B. burgdorferi B31 by tick bite. Whereas mice immunized with a soluble, nondenatured form continued to show protection rates close to 100%, mice that had been immunized with denatured antigen were not protected. Furthermore, mice that were immunized with an insoluble (rather than a soluble), nondenatured form of the recombinant OspC showed a protection rate of only 40%. Protective epitope localization experiments showed that either the amino or the carboxy end of the recombinant protein was required to react with a protective OspC-specific monoclonal antibody. The data from these experiments demonstrate that a conformational organization of the protein is essential for the protective capability of the strain B31 OspC immunogen.

scholarly journals The Dominant Epitope of Borrelia garinii Outer Surface Protein C Recognized by Sera from Patients with Neuroborreliosis Has a Surface-Exposed Conserved Structural Motif

1998 ◽  
Vol 66 (9) ◽  
pp. 4073-4079 ◽  
Author(s):  
Marianne J. Mathiesen ◽  
Arne Holm ◽  
Michael Christiansen ◽  
Jens Blom ◽  
Klaus Hansen ◽  
...  
Keyword(s):  
B Cells ◽  
Lyme Borreliosis ◽  
Outer Surface ◽  
Protein C ◽  
Surface Protein ◽  
Terminal Region ◽  
Structural Motif ◽  
High Avidity ◽  
Binding Studies ◽  
Outer Surface Protein

ABSTRACT Epitope mapping of outer surface protein C (OspC) by using sera from patients with neuroborreliosis led to the identification of one single major immunodominant epitope within the C-terminal 10 amino acid residues. Peptide binding studies and alanine replacement scanning of the C-terminal decapeptide, PVVAESPKKP, revealed a critical role for the PKKP sequence and its terminal carboxyl group for the binding of immunoglobulin M (IgM) antibodies from patients with Lyme borreliosis. Electron microscopy of antibody-labeled spirochetes indicated that the C-terminal region is exposed on the surface of the spirochete. Based on homology to proteins of known function, this region most probably adopts a polyproline II-like helix, which is found in surface-exposed structures involved in protein-protein interactions. This structural motif is highly conserved in Borrelia species causing Lyme borreliosis and subjected to purifying selection. We suggest that the abundance of the C-terminal region of OspC on the surface of B. burgdorferi allows a multimeric high-avidity interaction between the spirochete and surface Igs on B cells. The resulting cross-linking of surface Igs on B cells may induce a T-cell-independent B-cell activation without IgM-to-IgG switching, thus explaining the lack of IgG antibodies to OspC in neuroborreliosis.

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