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Development of an OspC-based tetravalent, recombinant, chimeric vaccinogen that elicits bactericidal antibody against diverse Lyme disease spirochete strains.

Abstract
Lyme disease is the most common arthropod-borne disease in North America and Europe. At present, there is no commercially available vaccine for use in humans. Outer surface protein C (OspC) has antigenic and expression characteristics that make it an attractive vaccine candidate; however, sequence heterogeneity has impeded its use as a vaccinogen. Sequence analyses have identified 21 well defined OspC phyletic groups or "types" (designated A-U). In this report we have mapped the linear epitopes presented by OspC types B, K, and D during human and murine infection and exploited these epitopes (along with the previously identified type A OspC linear epitopes) in the development of a recombinant, tetravalent, chimeric vaccinogen. The construct was found to be highly immunogenic in mice and the induced antibodies surface labeled in vitro cultivated spirochetes. Importantly, vaccination induced complement-dependent bactericidal antibodies against strains expressing each of the OspC types that were incorporated into the construct. These results suggest that an effective and broadly protective polyvalent OspC-based Lyme disease vaccine can be produced as a recombinant, chimeric protein.
AuthorsChristopher G Earnhart, Eric L Buckles, Richard T Marconi
JournalVaccine (Vaccine) Vol. 25 Issue 3 Pg. 466-80 (Jan 05 2007) ISSN: 0264-410X [Print] Netherlands
PMID16996663 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Epitopes
  • Lyme Disease Vaccines
  • Phosphatidylcholines
  • Vaccines, Synthetic
  • 1-oleoyl-2-stearoylphosphatidylcholine
Topics
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Borrelia burgdorferi (immunology, isolation & purification)
  • Cloning, Molecular
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes (immunology)
  • Fluorescent Antibody Technique
  • Immunoblotting
  • Lyme Disease (immunology, prevention & control)
  • Lyme Disease Vaccines (genetics, immunology)
  • Male
  • Mice
  • Mice, Inbred C3H
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphatidylcholines (genetics, immunology)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Species Specificity
  • Vaccines, Synthetic (genetics, immunology)

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