INABILITY OF TRUNCATED RECOMBINANT OSP-A PROTEINS TO ELICIT PROTECTIVE IMMUNITY TO BORRELIA-BURGDORFERI IN MICE

The murine immune response to Borrelia burgdorferi (Bb), the etiologic agent of Lyme disease, is characterized by the development of antibod ies reactive with the outer surface protein (Osp) A. It has been demon strated that passive immunization of mice with at least some Osp A ant ibodies, including an Osp A mAb (CIII.78) that binds to a conformation al epitope in the carboxyl-terminus of Osp A, provides protection agai nst Bb challenge. Active immunization of mice with Osp A also confers protection, making Osp A a candidate for a vaccine Ag. To determine th e regions of the Osp A protein that can elicit protective immunity, we immunized and boosted mice with overlapping recombinant truncated fra gments of Osp A, then challenged them with Bb. All groups of mice deve loped IgG Osp A antibodies detectable by immunoblotting with sera dilu ted at least 5000-fold. As expected, vaccination with full-length reco mbinant Osp A protected mice from challenge infection. In contrast, no ne of the mice vaccinated with the truncated Osp A proteins demonstrat ed immunity, even those immunized with an Osp A fragment binding the n eutralizing mAb CIII.78. Osp A antibodies contained in the truncated O sp A antisera also failed to immunoprecipitate in vitro translated ful l-length Osp A and did not bind, as demonstrated by indirect immunoflu orescence, to live or acetone-fixed Bb. Taken together, these results suggest that neutralizing Osp A antibodies are induced by vaccination with the full-length recombinant Osp A protein but not by vaccination with recombinant fragments.