Specific immune response to a synthetic peptide derived from outer surface protein C of Borrelia burgdorferi predicts protective borreliacidal antibodies

Abstract

In a previous study, we described the development of a new specific serodiagnostic test for Lyme disease involving enzyme-linked immunosorbent assay and a synthetic peptide, OspC-I. The OspC-I peptide is derived from part of the outer surface protein C (OspC) amino acid sequence of Borrelia burgdorferi and is located in the region conserved among B. burgdorferi sensu stricto or sensu lato isolates. In this study, we demonstrate that sera containing antibodies against OspC-I from patients with early Lyme disease had borreliacidal activity against isolates of three genospecies of Lyme disease spirochete, B. burgdoreferi B31, B. garinii HPI and B. afzelii HT61. However, the borreliacidal activity against B. burgdorferi, which has not been isolated in Japan, was weaker than that against the other species. Vaccination of mice with OspC-I induced the production of anti-OspC-I antibodies in serum with borreliacidal activity. The immune mouse serum had significantly higher levels of borreliacidal activity against HP1 and HT61, than against B31. Neutralization of borreliacidal activity with anti-IgM antibodies showed that the borreliacidal activity of anti-OspC-I antibodies in serum was due to IgM. Furthermore. mice vaccinated with OspC-I were protected against challenge with HPI and HT61. but not fully protected against infection with B31. These results suggest that OspC-I is not only a specific antigen for use in serodiagnostic tests for Lyme disease, but is also a potential candidate for a Lyme disease vaccine in Japan.

C-Terminal Region of Outer Surface Protein C Binds Borreliacidal Antibodies in Sera from Patients with Lyme Disease

“…Several investigators have shown that borreliacidal OspC antibodies are formed shortly after infection with B. burgdorferi (17,22,30). Our results confirmed these findings and showed that OspC borreliacidal antibodies in early Lyme disease sera were predominantly IgM or IgG.…”

“…It was extraordinary that adsorbing the early Lyme disease sera with OspC-Dra removed the entire concentration of OspC antibodies detected by the ELISA or Western blot. The OspC-Dra contained only the ␣5 helix and a small region of the ␣4 helix (12), and high concentrations of antibodies specific for regions (␣1 helix) near the N terminus have been observed in sera from patients with early Lyme disease (17). One would have expected these antibodies to remain detectable.…”

Application of Liposomes for Construction of Vaccines

“…Induction of OspC-specific opsonizing antibodies to non -lipidised OspC could be enhanced by appropriate adjuvants and carriers like such as various modification of liposomes. It was reported that immunisation of mice with non-lipidated OspC in strong adjuvants (Complete Freund's Adjuvant, TiterMax, or Alum) could induce intense OspCspecific antibody responses Gilmore et al, 1996;Gilmore and Mbow, 1999;Ikushima et al, 2000). Here we demonstrated that similarly strong response could be elicited by immunisation of experimental mice with metallochelating nanoliposomes with entrapped lipophilic derivatives of norAbu-MDP as a potent adjuvant molecule.…”

Diagnosis of Lyme Borreliosis

“…Presumably OspA and OspB are eventually expressed in mammals, since antibodies to these antigens can be detected during late infection (10, 84). Antibodies to OspA or OspB may be borreliacidal (46,132,286,287). OspA antibodies were readily generated after administration of the recombinant OspA vaccine, which was commercially available in the United States for use in humans until March 2002 (327).…”

“…(i) Functional antibodies: borreliacidal antibody assays. Antibodies to certain antigens of B. burgdorferi sensu lato, in particular to certain outer surface proteins, may have bactericidal activity (46,132,249,286,287). Borreliacidal antibodies have been used in the immunodiagnosis of early and late LB by a few centers (5,47,48).…”