Here is another structure of OspA, in complex with mouse mAb LA-2 . This structure was identified as having a protective B-cell epitope by NMR spectroscopic chemical shift perturbation and X-ray crystallographic analysis (3). This region overlaps and includes the aforementioned CTD epitope, shown to be protective in the infected host.
The LA-2 antibody, like mAb 4C10C2, has been shown to have its binding restricted to B.b. sensu stricto (US and European) strains of the spirochete, and fails to recognize strains from either Borrelia garinii or Borellia afzelii (Europe and Asia), despite the limited variability of the OspA sequence within strains. For burgdorferi sensu stricto and afzelii, two structurally non-conservative changes have been identified within the epitope, namely at Ala208 and Asn251 . For B. garinii, there is at least one such change, although others have been documented, specifically at Ala215, which becomes a lysine .
LA-2 equivalent antibodies have also been indentified as being protective, following vaccination with OspA. This is important because for antibodies to be effective in blocking spirochete transmission at the site of infection, serum levels of the antibody must be high enough to be detectable by methods like the ELISA. Detailed structural knowledge of such antibodies can be a powerful tool to both develop and refine vaccine strategies. Being able to define the epitope on the antigen to which such antibodies bind is also useful information for those purposes.
The high degree of conservation at this epitope, taken with the additional structural and antibody-binding data from the other monoclonals, supports the development of a multivalent OspA vaccine. Such a therapy would potentially be protective against the transmission of Lyme disease, and could be potentially useful in blocking infection by all strains of the spirochete. However, more research is clearly needed to fully determine to most effective course of action in the prevention of this disease.