VraA (BBI16) protein of Borrelia burgdorferi is a surface-exposed antigen with a repetitive motif that confers partial protection against experimental Lyme borreliosis.
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abstract
We have previously described the expression cloning of nine Borrelia burgdorferi antigens, using rabbit serum enriched for antibodies specific for infection-associated antigens, and determined that seven of these antigens were associated with infectious B. burgdorferi strain B31. One of these infection-associated antigens encoded a 451-amino-acid putative lipoprotein containing 21 consecutive and invariant 9-amino-acid repeat sequences near the amino terminus that we have designated VraA for virulent strain-associated repetitive antigen A. The vraA locus (designated BBI16 by The Institute for Genomic Research) maps to one of the 28-kb linear plasmids (designated lp28-4) that is not present in noninfectious strain B31 isolates. Subsequent PCR analysis of clonal isolates of B. burgdorferi B31 from infected mouse skin revealed a clone that lacked only lp28-4. Southern blot and Western blot analyses indicated that the lp28-4 and VraA proteins, respectively, were missing from this clone. We have also determined that VraA is a surface-exposed protein based on protease accessibility assays of intact whole cells. Furthermore, vraA expression is modestly derepressed when cells are grown at 37 degrees C relative to cells grown at 32 degrees C, suggesting that VraA is, in part, a temperature-inducible antigen. Homologues cross-reactive to B. burgdorferi B31 VraA, most with different molecular masses, were identified in several B. burgdorferi sensu lato isolates, including B. andersonii, suggesting that the immunogenic epitope(s) present in strain B31 VraA is conserved between Borrelia spp. In protection studies, only 8.3% of mice (1 of 12) immunized with full-length recombinant VraA fused to glutathione S-transferase (GST) were susceptible to infectious challenge with 10(2) B. burgdorferi strain B31, whereas naive mice or mice immunized with GST alone were infected 40% or 63 to 67% (depending on tissues assayed) of the time, respectively. As such, the partial protection elicited by VraA immunization provides an additional testable vaccine candidate to help protect against Lyme borreliosis.
