THE OUTER SURFACE PROTEIN-A (OSPA) OF BORRELIA-BURGDORFERI - A VACCINE CANDIDATE AND BIOACTIVE MEDIATOR

In the search for a suitable vaccine candidate for Lyme borreliosis th e principles of protective immunity were studied in a murine model of Borrelia burgdorferi infection, It was found that the spirochetal oute r surface protein A (lipOspA) in its native and recombinant lipidated form induces monospecific immune sera, which in passive transfer exper iments protect SCID mice against experimental and tick-borne infection and disease, These and similar findings of independent groups led to the development of a vaccine formulation containing lipOspA, When test ed in clinical phase I/II safety trials the recombinant lipOspA vaccin e was shown to be safe, immunogenic and able to elicit borreliacidal a ntibodies, At present, clinical phase III efficacy trials are being co nducted, B. burgdorferi infection involves the dissemination of the sp irochetes from the site of the tick bite, infection of distant organs, and induction of a chronic inflammatory process, Recent studies indic ate that the spirochetes may utilize host-derived enzyme systems to in crease their virulence/pathogenicity. It was found that lipOspA serves as a surface receptor for the host-derived proteolytic enzyme plasmin (ogen), the central component of the so-called plasminogen activator s ystem, Moreover, it was found that spirochetes are able to activate en dothelial cells and blood-derived leukocytes, such as monocytes/macrop hages, B cells and T cells, to express functions and/or secrete molecu les, which are known to promote inflammatory responses, Part of these activities were exerted by the isolated lipOspA, The studies indicate an important role of lipOspA, both for the induction of a protective i mmune response by the host, as well as for the pathogenic processes el icited during B, burgdorferi infection.