An Octavalent Lyme Disease Vaccine Induces Antibodies That Recognize All Incorporated ospC Type-Specific Sequences

Abstract

Lyme disease is the most common vector-borne disease in North America and Europe and, if untreated, has significant arthritic, cardiac, dermatological and neurological sequelae. There is no currently available human Lyme disease vaccine. Outer surface protein C, because of its antigenicity, protective ability, and expression characteristics has emerged as a promising second generation vaccine candidate; however, significant sequence heterogeneity has impeded its development. Analyses of OspC sequences have revealed the existence of stable phylogenetic clusters or types, and that the type-defining sequence variation occurs within defined domains of the protein. Recent data indicating that immunodominant, and potentially protective OspC epitopes are located in these hypervariable regions has allowed development of a tetravalent, epitope-based, chimeric vaccine. In this report, we have extended that previously described tetravalent construct to include four additional OspC types. We demonstrate that the construct is highly immunogenic, and elicits type-specific antibodies that recognize each of the eight incorporated OspC type-specific epitopes. Antibody raised to the octavalent construct readily binds to the surface of strains expressing each component OspC type, indicating that the incorporated epitopes are presented on the surface of intact cells. In addition, the construct elicits antibody isotypes associated with complement-dependent bactericidal activity. These results represent an important step forward in the design of a broadly protective polyvalent OspC-based Lyme disease vaccine.

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

“…OspA was the immunogen of choice because it is a proven vaccine candidate against B. burgdorferi via the parenteral route (16,18) in addition to inducing a protective immune response when administered orally as purified antigen (34) or as recombinant Escherichia coli (17,21). Although there have been many studies to find additional vaccine candidates for Lyme disease (5,12,13,19,20,25,48), OspA is still the most effective immunogen against this pathogen. Following the discovery of a controversial autoantigenic epitope in OspA (24), we substituted this epitope in its sequence before cloning it into L. plantarum.…”

The Borrelia hermsii Factor H Binding Protein FhbA Is Not Required for Infectivity in Mice or for Resistance to Human Complement In Vitro

“…After 2, 6, and 24 h, cell viability was assessed using the BacLight LIVE/DEAD kit (Invitrogen) and fluorescence microscopic counts of cells in 10 fields under ϫ400 magnification. Methods for staining and microscopy were as described in earlier publications (37). Data are presented as percent survival, calculated as follows: (average number of intact cells/number of intact and disrupted cells per 10 ϫ400-magnification fields of view) ϫ 100.…”

“…ELISA plates were coated with a suspension of wild-type B. hermsii YOR cells and screened with serial dilutions of serum collected from each mouse. All methods were as previously described (37).…”

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

“…More than 30 phylogenetically distinct types of OspC have been defined (4, 11, 51). It has been hypothesized that OspC and its relapsing fever Borrelia ortholog (Vsp) form arrays in the outer membrane (30, 52).OspC is a candidate for a next-generation Lyme disease vaccine (11,12,15,28). The surface presentation of OspC may have implications for vaccine design.…”

“…OspC is a candidate for a next-generation Lyme disease vaccine (11,12,15,28). The surface presentation of OspC may have implications for vaccine design.…”