Development of a multivalent vaccine for mouse reservoirs of deer tick pathogens

． 在美国，蜱虫是三种人类感染的媒介——莱姆病、巴贝斯虫病和人粒细胞埃利希体病。这三种疾病的发病率在过去十年中一直在增加。尽管感染后可以使用抗生素治疗，但这些疾病中的每一种都与显著的发病率有关，在某些情况下甚至与死亡率有关。针对人类疾病的预防措施在很大程度上仅限于避免蜱虫的方法，目前没有针对任何疾病的人类疫苗。预防人类疾病的另一种策略是开发治疗方法，以减少这些病原体在其野生宿主、蜱虫和白足鼠等小型啮齿动物中的携带和传播。本实验室以伯氏疏螺旋体外表面a （OspA）蛋白为基础，为白足鼠研制了基于牛痘病毒（VV）的抗伯氏疏螺旋体疫苗。虽然这一策略显示出了希望，但对小鼠的OspA疫苗的保护仅限于莱姆病。其他研究人员最近取得的进展显示了开发抗蜱虫疫苗的潜力。接种带有蜱抗原的动物疫苗已被证明可减少蜱的摄食和感染，和/或减少蜱传播和感染病原体。在这项提议中，我们将测试在VV载体中表达的蜱虫抗原在口服小鼠时对蜱虫侵扰和疾病传播的保护能力。鉴定抗蜱虫靶点将使我们能够开发一种含有蜱虫和病原体抗原的多价疫苗，以进一步减少宿主动物中蜱虫传播的疾病。这个项目的总体目标是转化，我们将尝试利用科学认识方面的最新进展，并将其应用于开发一种疫苗，这种疫苗可以通过减少野生动物宿主的疾病，直接影响人类和蜱虫传播疾病的发病率。

. Ixodes ticks serve as the vector for 3 human infections in the U.S.-- Lyme disease, Babesiosis and human granulocytic ehrlichiosis. The incidence of all three diseases has been increasing over the last decade. Despite the availability of antibiotic therapy after infection, each of these diseases is associated with significant morbidity or, in some cases, even mortality. Preventative measures targeted towards human disease have been largely limited to tick avoidance methods and there are currently no human vaccines available for any of the diseases. An alternative strategy for prevention of human disease would be to develop treatments to reduce carriage and transmission of these pathogens in their wild reservoirs, Ixodes ticks and small rodents such as white-footed mice. Our laboratory has been involved in developing a vaccinia virus (VV) based anti-Borrelia burgdorferi vaccine for white-footed mice based on the outer surface A (OspA) protein of B. burgdorferi. While this strategy has shown promise, protection from an OspA vaccine for mice is limited to Lyme disease. Recent progress by other investigators has shown the potential for the development of anti-tick vaccines. Vaccination of animals with tick antigens has been shown to decrease feeding and infestation by ticks and/or to decrease transmission and acquisition of infectious agents by ticks. In this proposal, we will test tick antigens expressed in a VV vector for their ability to protect against tick infestation and disease transmission when administered orally to mice. Identification of anti-tick targets will allow us to develop a multivalent vaccine containing both tick and pathogen antigens for improved reduction of tick borne diseases in reservoir animals. The overall goal of this project is translational, in that, we will attempt to make use of recent advances in scientific understanding and apply them towards the development of a vaccine that could have a direct impact on the incidence of human, tick transmitted diseases through reduction of disease in wildlife reservoirs. The tick-borne infections, Lyme disease, Ehrlichiosis and Babesiosis, are significant public health problems in the U.S. One potential approach to the control of these diseases is to reduce carriage of the organisms in their wild-life reservoirs. In this proposal, we outline a strategy to develop an ecologically targeted vaccine that blocks transmission of these pathogens between tick and mammalian reservoirs through inhibition of tick feeding, thus reducing human infections by reducing the numbers of infected ticks.