Lyme disease, or Lyme borreliosis, the most prevalent arthropod-borne disease in the Western world, is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group and is predominantly transmitted through Ixodes ticks. There is currently no vaccine available to prevent Lyme borreliosis in humans. Borrelia outer membrane proteins are reviewed which have been investigated as vaccine candidates. In addition, several tick proteins are discussed, on which anti-tick vaccines have been based, or are interesting future candidates, to prevent transmission of the spirochete from the tick vector to the mammalian host. Finally, novel vaccination strategies to prevent Lyme borreliosis are proposed, based on multiple Borrelia antigens, tick antigens or a combination of both Borrelia as well as tick antigens.
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