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

.硬蜱是美国三种人类感染的媒介--莱姆病、巴贝斯虫病和人粒细胞埃里希体病。在过去十年中，这三种疾病的发病率都在上升。尽管在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相关，或者在某些情况下，甚至与死亡率相关。针对人类疾病的预防措施在很大程度上限于避免蜱虫的方法，目前没有针对任何疾病的人用疫苗。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、硬蜱和小型啮齿动物（如白足小鼠）中的携带和传播。我们的实验室已经参与了基于B的外表面A（OspA）蛋白的白足小鼠的基于牛痘病毒（VV）的抗伯氏疏螺旋体疫苗的开发。伯格多费里。虽然这种策略已经显示出希望，但OspA疫苗对小鼠的保护仅限于莱姆病。其他研究人员的最新进展显示了开发抗蜱疫苗的潜力。已显示用蜱抗原对动物进行疫苗接种可减少蜱的摄食和侵染和/或减少蜱传播和获得传染性病原体。在本提案中，我们将测试VV载体中表达的蜱抗原在经口给予小鼠时防止蜱侵染和疾病传播的能力。抗蜱靶标的鉴定将使我们能够开发含有蜱和病原体抗原的多价疫苗，用于改善储库动物中蜱传播疾病的减少。该项目的总体目标是转化，因为我们将尝试利用科学认识的最新进展，并将其应用于疫苗的开发，通过减少野生动物宿主中的疾病，对人类蜱传播疾病的发病率产生直接影响。 蜱传播的感染，莱姆病，埃里希体病和巴贝西虫病，是美国的重大公共卫生问题。控制这些疾病的一种潜在方法是减少野生动物宿主中生物的携带。在这项提案中，我们概述了一项战略，以开发一种生态靶向疫苗，通过抑制蜱虫进食来阻断这些病原体在蜱虫和哺乳动物宿主之间的传播，从而通过减少受感染蜱虫的数量来减少人类感染。

. 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.