Vector-targeting CLP-vaccines against tick-transmitted infections

点击翻译按钮获取中文摘要

Many severe infectious diseases of humans caused by bacteria, viruses and protozoa are transmittedby arthropod vectors. This includes the tick-transmitted spirochete Borrelia burgdorferi (Bb), thecausative agent of Lyme disease. Tick saliva contains a cocktail of immunosuppressive factors thatare essential for successful tick feeding but which are also exploited by tick-borne pathogens toenhance their own transmission. One such factor is the recently characterized Ixodes (I.) scapularistick saliva protein Salp15, which potentiates transmission of Bb by generally inhibiting the hosts’ Thelper cell activity and, in addition, by specifically binding to the Bb outer surface protein OspC,providing a camouflage coat for the bacteria when they enter the mammalian host. The aim of thisproject is to induce neutralizing antibody responses to Salp15 and to analyze their potential to blockBb transmission and subsequent infection in mice. To overcome the immunosuppressive activity ofSalp15, we propose to use hepatitis B virus capsid-like particles (CLPs) as a potent immuneenhancingprotein antigen presentation system. Because the structure of Salp15 is unknown, we willtake advantage of a novel version of this CLP system that allows for the surface display of full-lengthproteins as immunogens largely independent of their native structure. Joining the complementaryexpertises of three laboratories, the respective Salp15-CLPs will be generated, characterized, andused to immunize mice. The protective potential of the specific antibodies will be determined inestablished mouse models of Bb infection. This work should open new avenues to protect against Bbinfection but beyond should provide information on the applicability of anti-vector vaccines as a novelstrategy to control arthropode-borne pathogens in general.