title: Evaluation of OspA vaccination-induced serological correlates of protection against Lyme borreliosis in a mouse model.
abstract: BACKGROUND
  For clinical development of a novel multivalent OspA vaccine against Lyme borreliosis, serological assays are required which can be used to establish immune correlates of protection against infection with Borrelia.
  
  
  METHODS
  Four assays (an OspA IgG ELISA, a competitive inhibition (CI) ELISA, a Borrelia surface-binding (SB) assay and a Borrelia killing assay) were used to evaluate the correlation between immune responses induced by rOspA 1/2 (a chimeric immunogen containing protective epitopes from OspA serotypes 1 and 2), and protective immunity against infection by B. burgdorferi s.s. (OspA-1) and B. afzelii (OspA-2). Mice were immunized with OspA 1/2 doses ranging from 0.3 ng to 100 ng, to induce a range of OspA antibody titers, and exposed to needle challenge with B. burgdorferi s.s. or tick challenge with B. afzelii. Receiver operator characteristics (ROC) curves were constructed for each assay, and the area under the curve (AUC), sensitivity, specificity and Youden Index were calculated. Potential cutoff antibody titers which could be used as correlates of vaccine-induced protection were derived from the maximum Youden Index.
  
  
  RESULTS
  Immunization with OspA-1/2 provided dose-dependent protection against infection with B. burgdorferi s.s. and B. afzelii. Antibody responses detected by all four assays were highly significantly correlated with protection from infection by either B. burgdorferi s.s. (p<0.0001 to 0.0062) or B. afzelii (p<0.0001). ROC analyses of the diagnostic effectiveness of each assay showed the AUC to range between 0.95 and 0.79, demonstrating that all assays distinguish well between infected and non-infected animals. Based on sensitivity, specificity and AUC, the OspA IgG ELISA and SB assays best discriminated between infected and non-infected animals.
  
  
  CONCLUSIONS
  All four assays differentiate well between Borrelia-infected and non-infected animals. The relatively simple, high throughput IgG ELISA would be suitable to establish immune correlates of protection for the novel OspA vaccine in clinical trials.
authors.affiliation: Vaccine R&D, Baxter BioScience, Orth/Donau, Austria.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schwendinger
authors.forename: Maria
authors.initials: M
authors.lastname: O'Rourke
authors.forename: Andreas
authors.initials: A
authors.lastname: Traweger
authors.forename: Helga
authors.initials: H
authors.lastname: Savidis-Dacho
authors.forename: Andreas
authors.initials: A
authors.lastname: Pilz
authors.forename: Daniel
authors.initials: D
authors.lastname: Portsmouth
authors.forename: Ian
authors.initials: I
authors.lastname: Livey
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
authors.forename: Brian A
authors.initials: BA
authors.lastname: Crowe
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D025065:Borrelia burgdorferi / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology*; D008193:Lyme Disease / Q000276:immunology / Q000517:prevention & control*; D022123:Lyme Disease Vaccines / Q000276:immunology*; D051379:Mice; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein