Comparison of Protection in Rabbits against Host-Adapted and CultivatedBorrelia burgdorferifollowing Infection-Derived Immunity or Immunization with Outer Membrane Vesicles or Outer Surface Protein A

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Abstract
In this study, infection-derived immunity in the rabbit model of Lyme disease was compared to immunity following immunization with purified outer membrane vesicles (OMV) isolated fromBorrelia burgdorferiand recombinant outer surface protein A (OspA). Immunization of rabbits with OMV isolated from virulent strain B31 and its avirulent derivative B313 (lacking OspA and DbpA) conferred highly significant protection against intradermal injection with 6 × 104in vitro-cultivated virulentB. burgdorferi. This is the first demonstration of protective immunogenicity induced by OMV. While immunization with OspA and avirulent B31 OMV provided far less protection against this challenge, rabbits with infection-derived immunity were completely protected. Protection against host-adaptedB. burgdorferiwas assessed by implantation of skin biopsies taken from rabbit erythema migrans (a uniquely rich source ofB. burgdorferiin vertebrate tissue) containing up to 108spirochetes. While all of the OMV- and OspA-immunized rabbits were fully susceptible to skin and disseminated infection, rabbits with infection-derived immunity were completely protected. Analysis of the antibody responses to outer membrane proteins, including DbpA, OspA, and OspC, suggests that the remarkable protection exhibited by the infection-immune rabbits is due to antibodies directed at antigens unique to or markedly up-regulated in host-adaptedB. burgdorferi.

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