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 the principles of protective immunity were studied in a murine model of Borrelia burgdorferi infection. It was found that the spirochetal outer surface protein A (lipOspA) in its native and recombinant lipidated form induces monospecific immune sera, which in passive transfer experiments 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 tested in clinical phase I/II safety trials the recombinant lipOspA vaccine was shown to be safe, immunogenic and able to elicit borreliacidal antibodies. At present, clinical phase III efficacy trials are being conducted. B. burgdorferi infection involves the dissemination of the spirochetes from the site of the tick bite, infection of distant organs, and induction of a chronic inflammatory process. Recent studies indicate that the spirochetes may utilize host-derived enzyme systems to increase 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 system. Moreover, it was found that spirochetes are able to activate endothelial cells and blood-derived leukocytes, such as monocytes/macrophages, B cells and T cells, to express functions and/or secrete molecules, 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 immune response by the host, as well as for the pathogenic processes elicited during B. burgdorferi infection.
Kramer
M D
MD
Institut für Immunologie, Universität Heidelberg, Germany.
Wallich
R
R
Simon
M M
MM
D000328:Adult; D000818:Animals; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D015748:Borrelia burgdorferi Group / Q000737:chemistry* / Q000276:immunology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D007116:Immunization, Passive; D007249:Inflammation / Q000378:metabolism; D008074:Lipoproteins; D008193:Lyme Disease / Q000201:enzymology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D051379:Mice; D016513:Mice, SCID; D010958:Plasminogen / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology
D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008074:Lipoproteins; C072045:OspA protein; D014614:Vaccines, Synthetic; D010958:Plasminogen