Borreliacidal OspC antibodies specific for a highly conserved epitope are immunodominant in human lyme disease and do not occur in mice or hamsters

Abstract

Humans produce highly specific borreliacidal antibodies against outer surface protein C (OspC) shortly after infection with Borrelia burgdorferi sensu stricto. We previously demonstrated the epitope recognized by immunoglobulin M (IgM) and IgG OspC borreliacidal antibodies was located within the 50 amino acids nearest the carboxy (C) terminus. In this study, we show the immunodominant epitope is located in the highly conserved region within the seven C-terminal amino acids. Six early Lyme disease sera that contained borreliacidal activity and IgM and/or IgG OspC antibodies were chosen randomly and adsorbed with truncated OspC containing the 16 or 7 amino acids nearest the C terminus. Adsorptions with each truncated protein abrogated the borreliacidal activity completely. In addition, only small concentrations of OspC antibodies remained detectable by enzyme-linked immunosorbent assay and Western blotting. Moreover, borreliacidal OspC antibodies were not induced in laboratory mice or hamsters despite heavy infections with B. burgdorferi spirochetes. These findings confirm that borreliacidal antibodies comprise the majority of the IgM and IgG OspC antibody response in human Lyme disease and that the epitope is located in the highly conserved C terminus. In addition, rodent animal models appear to be inappropriate subjects for assessing the effectiveness of the epitope for serodiagnosis or as a human Lyme disease vaccine.

FIG. 1.

Representative Western blots of antibodies in an early Lyme disease serum reactive against B. burgdorferi 50772 before adsorptions (lanes 1) and after adsorptions with OspC (lanes 2), C16 (lanes 3), or C7 (lanes 4). Panels A and B are IgM and IgG Western blots, respectively. Note that the effects of the adsorptions on the detection of OspC antibodies in the other four sera were identical.

FIG. 2.

Western blots of pooled (n = 5) hamster immune serum before (lane B) and after (lane C) adsorptions with OspC or pooled (n = 5) mouse immune serum before (lane D) and after (lane E) adsorptions with OspC. Lane A shows reactivity by polyclonal antibodies specific for OspC.