Development of an OspC-based tetravalent, recombinant, chimeric vaccinogen that elicits bactericidal antibody against diverse Lyme disease spirochete strains.
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.
Earnhart
Christopher G
CG
Department of Microbiology and Immunology, Medical College of Virginia at Virginia Commonwealth University, Richmond, VA 23298-0678, USA.
Buckles
Eric L
EL
Marconi
Richard T
RT
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D025065:Borrelia burgdorferi / Q000276:immunology* / Q000302:isolation & purification; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D008193:Lyme Disease / Q000276:immunology* / Q000517:prevention & control*; D022123:Lyme Disease Vaccines / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010713:Phosphatidylcholines / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D022123:Lyme Disease Vaccines; D010713:Phosphatidylcholines; D014614:Vaccines, Synthetic; C067973:1-oleoyl-2-stearoylphosphatidylcholine