scholarly journals 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

2006 ◽  
Vol 13 (10) ◽  
pp. 1162-1165 ◽  
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.

scholarly journals Demonstration of OspC Type Diversity in Invasive Human Lyme Disease Isolates and Identification of Previously Uncharacterized Epitopes That Define the Specificity of the OspC Murine Antibody Response

2005 ◽  
Vol 73 (12) ◽  
pp. 7869-7877 ◽  
Author(s):  
Christopher G. Earnhart ◽  
Eric L. Buckles ◽  
John Stephen Dumler ◽  
Richard T. Marconi
Keyword(s):  
Lyme Disease ◽  
Antibody Response ◽  
Virulence Factor ◽  
Vaccine Development ◽  
Antigenic Structure ◽  
Detailed Knowledge ◽  
Invasive Infection ◽  
Variable Nature ◽  
Invasive Infections ◽  
Important Virulence Factor

ABSTRACT Outer surface protein C (OspC) of the Lyme disease spirochetes is an important virulence factor that has potential utility for vaccine development. Of the 21 OspC types that have been identified, it has been postulated that types A, B, I, and K are specifically associated with invasive infections. Through an analysis of isolates collected from patients in Maryland we found that OspC types C, D, and N are also associated with invasive infections. This observation suggests that there is greater diversity in the group of OspC types associated with invasive infection than has been previously suggested. Detailed knowledge of the antigenic structure of OspC is essential for vaccine development. To determine if the antibody response to OspC is type specific, recombinant proteins of several different OspC types were immunoblotted and screened with sera from mice infected with isolates having known OspC types. These analyses revealed a high degree of specificity in the antibody response and suggested that the immunodominant epitopes of OspC reside in the variable domains of the protein. To localize these epitopes, OspC fragments were generated and screened with serum collected from infected mice. These analyses led to identification of previously uncharacterized epitopes that define the type specificity of the OspC antibody response. These analyses provide important insight into the antigenic structure of OspC and also provide a basis for understanding the variable nature of the antibody response to this important virulence factor of the Lyme disease spirochetes.

scholarly journals Disulfide-Mediated Oligomer Formation in Borrelia burgdorferi Outer Surface Protein C, a Critical Virulence Factor and Potential Lyme Disease Vaccine Candidate

2011 ◽  
Vol 18 (6) ◽  
pp. 901-906 ◽  
Author(s):  
Christopher G. Earnhart ◽  
DeLacy V. L. Rhodes ◽  
Richard T. Marconi
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Disulfide Bonds ◽  
Vaccine Candidate ◽  
Site Directed Mutagenesis ◽  
Yield Strain ◽  
Content Type ◽  
Oligomer Formation ◽  
Lyme Disease Vaccine

ABSTRACTBorrelia burgdorferiOspC is an outer membrane lipoprotein required for the establishment of infection in mammals. Due to its universal distribution amongB. burgdorferisensu lato strains and high antigenicity, it is being explored for the development of a next-generation Lyme disease vaccine. An understanding of the surface presentation of OspC will facilitate efforts to maximize its potential as a vaccine candidate. OspC forms homodimers at the cell surface, and it has been hypothesized that it may also form oligomeric arrays. Here, we employ site-directed mutagenesis to test the hypothesis that interdimeric disulfide bonds at cysteine 130 (C130) mediate oligomerization.B. burgdorferiB31ospCwas replaced with a C130A substitution mutant to yield strain B31::ospC(C130A). Recombinant protein was also generated. Disulfide-bond-dependent oligomer formation was demonstrated and determined to be dependent on C130. Oligomerization was not required forin vivofunction, as B31::ospC(C130A) retained infectivity and disseminated normally. The total IgG response and the induced isotype pattern were similar between mice infected with untransformed B31 and those infected with the B31::ospC(C130A) strain. These data indicate that the immune response to OspC is not significantly altered by formation of OspC oligomers, a finding that has significant implications in Lyme disease vaccine design.

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

2014 ◽  
Vol 1 (suppl_1) ◽  
pp. S354-S354
Author(s):  
Elzbieta Jacek ◽  
Lars Komorowsky ◽  
Mary Ajamian ◽  
Brad Kim ◽  
Gary P. Wormser ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Antibody Response

scholarly journals Characterization of a Borrelia burgdorferi VlsE Invariable Region Useful in Canine Lyme Disease Serodiagnosis by Enzyme-Linked Immunosorbent Assay

2000 ◽  
Vol 38 (11) ◽  
pp. 4160-4166 ◽  
Author(s):  
Fang Ting Liang ◽  
Richard H. Jacobson ◽  
Reinhard K. Straubinger ◽  
Amy Grooters ◽  
Mario T. Philipp
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Antibody Response ◽  
Immunosorbent Assay ◽  
Protein A ◽  
Immunoblot Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Entire Study ◽  
Variable Surface

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.

scholarly journals Decorin-Binding Protein A (DbpA) of Borrelia burgdorferi Is Not Protective When Immunized Mice Are Challenged via Tick Infestation and Correlates with the Lack of DbpA Expression by B. burgdorferi in Ticks

2000 ◽  
Vol 68 (8) ◽  
pp. 4759-4764 ◽  
Author(s):  
Kayla E. Hagman ◽  
Xiaofeng Yang ◽  
Stephen K. Wikel ◽  
George B. Schoeler ◽  
Melissa J. Caimano ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Murine Model ◽  
Blood Meal ◽  
Tick Infestation ◽  
Ixodes Scapularis ◽  
Binding Protein ◽  
Protein A ◽  
Lyme Disease Vaccine

ABSTRACT Previous studies showed that decorin-binding protein A (DbpA) ofBorrelia burgdorferi was a protective immunogen in the murine model of Lyme borreliosis when mice were challenged (needle inoculated) intradermally with in vitro-cultivated spirochetes. In the present study, DbpA-immunized C3H/HeJ mice were not protected from infection when infested with Ixodes scapularis nymphs harboring virulent B. burgdorferi 297. This lack of protection correlated with the failure to detect DbpA on B. burgdorferi in ticks, suggesting that DbpA is not available as a target for bactericidal antibodies in serum when B. burgdorferi-infected ticks take their blood meal from an immunized host. The failure of DbpA immunization to protect tick-challenged mice contradicts the results of earlier needle inoculation vaccination experiments and suggests that DbpA may not be suitable as a Lyme disease vaccine.

scholarly journals Borrelia burgdorferi RST1 (OspC Type A) Genotype Is Associated with Greater Inflammation and More Severe Lyme Disease

2011 ◽  
Vol 178 (6) ◽  
pp. 2726-2739 ◽  
Author(s):  
Klemen Strle ◽  
Kathryn L. Jones ◽  
Elise E. Drouin ◽  
Xin Li ◽  
Allen C. Steere
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Type A

scholarly journals Borrelia burgdorferi BBA52 is a potential target for transmission blocking Lyme disease vaccine

Vaccine ◽  
2011 ◽  
Vol 29 (48) ◽  
pp. 9012-9019 ◽  
Author(s):  
Manish Kumar ◽  
Simarjot Kaur ◽  
Toru Kariu ◽  
Xiuli Yang ◽  
Ioannis Bossis ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Transmission Blocking ◽  
Potential Target ◽  
Lyme Disease Vaccine
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