Borrelia burgdorferi Outer surface protein A (OspA): A tick transmission factor and a Lyme disease vaccine

Borrelia burgdorferi, the etiologic agent of Lyme disease, is the leading cause of vector-borne disease in the United States and Europe. The bacteria are transmitted by ticks in the Ixodes ricinus complex. A vaccine based on Outer surface protein A (OspA), an outer membrane lipoprotein, has been shown to effectively prevent transmission of the spirochete from ticks to mammalian hosts. Antibodies enter the gut of the feeding tick during the bloodmeal, and interact with the bacteria in a manner that inhibits migration of spirochetes to the host. We used alpha-OspA antibodies to better understand the dynamics of transmission, to examine how antibodies block transmission, and sought alternative delivery mechanisms to improve OspA vaccine efficacy.; We determined that the ability of a neutralizing alpha-OspA monoclonal antibody to block transmission was not dependent on host complement. In addition, Fab' fragments of this antibody were capable of preventing transmission. The lack of reduction in bacterial load within ticks between test and control groups reveals that reduction in numbers is not required to prevent transmission. The antibody bound to the bacteria within the tick midgut and prevented the expression of another outer surface protein, OspC. We propose that the inhibition of expression of OspC by alpha-OspA antibodies binding leads to a block in transmission of B. burgdorferi.; Venezuelan equine encephalitis virus replicon particles (VRP) encoding B. burgdorferi OspA were evaluated for their ability to induce an immune response and provide protection from tick-borne spirochetes. VRP expressing ospA that accumulated intracellularly or was secreted from host cells were tested. Mammalian cells modified the secreted form of the bacterial protein by adding N-linked glycans. Mutants of the secreted form of ospA were produced that lacked the glycosylation sequences. Mice vaccinated with VRP expressing secreted OspA produced significant amounts of anti-OspA antibodies, whereas VRP expressing intracellular OspA were less immunogenic. The secreted constructs induced an immune response that reduced the bacterial load in feeding Ixodes scapularis and blocked transmission to the host. These results indicate that VRP are capable of providing protection against tick-borne B. burgdorferi, and potentially can be used for developing improved vaccines against Lyme disease.