Comparison of protection in rabbits against host-adapted and cultivated Borrelia burgdorferi following infection-derived immunity or immunization with outer membrane vesicles or outer surface protein A

In this study, infection-derived immunity in the rabbit model of Lyme disea se was compared to immunity following immunization with purified outer memb rane vesicles (OMV) isolated from Borrelia burgdorferi and recombinant oute r surface protein A (OspA). Immunization of rabbits with OMV isolated from virulent strain B31 and its avirulent derivative B313 (lacking OspA and Dbp A) conferred highly significant protection against intradermal injection wi th 6 x 10(4) in vitro-cultivated virulent B. burgdorferi. This is the first demonstration of protective immunogenicity induced by OMV, While immunizat ion with OspA and avirulent B31 OMV provided far less protection against th is challenge, rabbits with infection-derived immunity were completely prote cted. Protection against host-adapted B. burgdorferi was assessed by implan tation of skin biopsies taken from rabbit erythema migrans (a uniquely rich source of B. burgdorferi in vertebrate tissue) containing up to 10(8) spir ochetes. While all of the OMV- and OspA-immunized rabbits were fully suscep tible to skin and disseminated Infection, rabbits with infection-derived im munity were completely protected. Analysis of the antibody responses to out er membrane proteins, including DbpA, OspA, and OspC, suggests that the rem arkable protection exhibit ed by the infection-immune rabbits Is due to ant ibodies directed at antigens unique to or markedly up-regulated in host-ada pted B. burgdorferi.