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**Outer surface protein A (OspA)** is an abundant, immunogenic lipoprotein found on the outer membrane of *Borrelia burgdorferi*, the spirochete responsible for Lyme disease[1][2][5]. Structurally, OspA is characterized by a dumbbell-shaped fold with two globular domains connected by a single-layer β-sheet, and is anchored to the outer membrane via an N-terminal lipid modification[2][4][5]. OspA is not typically expressed in mammalian hosts but is upregulated when the bacteria inhabit the tick vector, where it mediates adherence to the tick midgut and supports bacterial survival during non-feeding and feeding cycles[4][8]. OspA serves as an effective antigen for blocking Lyme disease transmission, as evidenced by the development of recombinant OspA-based vaccines that elicit protective antibodies in mammals, blocking transmission by neutralizing spirochetes in the tick midgut before they can infect the host[8]. Safety challenges to OspA-based vaccines include concerns about antigenic heterogeneity among Borrelia species and a theoretical risk of autoimmune complication, though this has not been conclusively demonstrated. OspA antibody responses can serve as biomarkers for vaccine-induced immunity but are not reliable for detection of active Lyme disease in humans due to its downregulation during mammalian infection phases[8].
Vaccines: Induction of protective antibodies that prevent transmission from tick to mammal host by targeting and neutralizing OspA-expressing spirochetes
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