Rocky Mountain Spotted Fever Vaccine Development

落基山斑疹热疫苗开发

• 批准号: 10814647
• 负责人: ROMAN R. GANTA
• 金额: $ 75.61万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10814647
• 关键词: Rocky; Mountain; Spotted; Fever; Vaccine

PROJECT SUMMARY: Tick-transmitted rickettsial diseases of the genera Anaplasma, Ehrlichia, and Rickettsia remain a growing public health concern in the USA and many parts of the world. The diseases include one of the oldest known rickettsial diseases, Rocky Mountain spotted fever (RMSF) caused by Rickettsia rickettsii. RMSF remains a serious disease of people and continues to be a public health concern in the USA and several North, Central and South American countries. Clinical signs of RMSF include fever, headache, nausea, vomiting, muscle pain, lack of appetite, and rash. The disease can progress rapidly to a life-threatening illness in untreated patients, resulting in high mortality rates ranging from 30-80%. During the last two decades, reported RMSF cases continue rising in parts of North America. Tick-borne diseases (TBDs) require the interplay of humans, ticks and reservoir animal hosts. We believe that developing a vaccine to prevent the disease can be accomplished by engaging in collaborative research with a team of experts having diverse expertise and yet having common broad research interests. Since dogs develop disease similar to people, a vaccine to prevent the disease in this host will most likely be effective in controlling the disease spread from wildlife, ticks and also infections from dogs to people. We recently tested two experimental vaccines; a subunit vaccine, which included two R. rickettsii recombinant proteins (RCA) and a whole cell inactivated antigen vaccine (WCA), to confer protection against virulent R. rickettsii infection challenge. WCA offered complete protection against RMSF, while RCA did not. This prior published work offers a strong scientific premise for the proposed detailed investigation. In particular, we aim to further characterize WCA in determining A) the duration of protection, B) the role of adjuvants in defining protection, C) the type of immune response observed, and D) the protection against tick transmitted homologous and heterologous challenges. We believe that this project, supported by strong scientific premise, addresses a significant public health problem. The goals are innovative as we will be the first group to investigate RMSF vaccine development using a physiologically relevant animal- tick-pathogen infection model. The central hypothesis of our application is that WCA protects against lethal RMSF caused by blood- and tick-borne infections, resulting from geographically distant pathogen strains, by stimulating immune protection for one year or longer. The specific aims of this application are: 1) Evaluate inactivation methods for preparing WCA and adjuvants in defining the vaccine protection. 2) Evaluate WCA protection against tick-transmitted challenges. 3) Evaluate WCA protection against R. rickettsii heterologous strain infection challenges. At the conclusion of this project, we expect that our efforts will translate to a fully developed vaccine, which is efficacious in an animal model known to naturally acquire R. rickettsii infections from an infected tick leading to life-threatening RMSF. We believe that achieving goals of this application will pave the way for extending vaccine studies to protect people from this lethal disease in the very near future.

项目摘要： tick虫的静电症的立体疾病，Ehrlichia和Rickettsia仍然在增长 美国和世界许多地区的公共卫生关注。这些疾病包括已知最古老的疾病之一 立克疾病，落基山斑点发烧（RMSF）由立克人士立克斯（Rickettsia Rickettsii）引起。 RMSF仍然是一个 人们的严重疾病，在美国和几个北部，继续成为公共卫生问题 和南美国家。 RMSF的临床体征包括发烧，头痛，恶心，呕吐，肌肉 疼痛，食欲不振和皮疹。该疾病可以迅速发展为未经治疗的威胁生命的疾病 患者的死亡率高30-80％。在过去的二十年中，RMSF报道 案件在北美部分地区继续增加。 tick传播疾病（TBD）需要人类的相互作用， tick和水库动物宿主。我们认为，开发以防止这种疾病的疫苗可能是 通过与具有多样专业知识的专家团队进行合作研究来完成 具有共同的广泛研究兴趣。由于狗会形成类似于人的疾病，因此可以预防一种疫苗 该宿主中的疾病很可能有效地控制着从野生动植物，tick虫和 从狗到人的感染。我们最近测试了两种实验疫苗。亚基疫苗，该疫苗 包括两种R. rickettsii重组蛋白（RCA）和一个全细胞灭活的抗原疫苗（WCA） 赋予对有毒的R. Rickettsii感染挑战的保护。 WCA提供了完全保护 RMSF，而RCA没有。这项先前发表的工作为拟议中的科学前提提供了强大的科学前提 详细研究。特别是，我们旨在进一步表征WCA在确定a）持续时间 保护，b）佐剂在定义保护中的作用，c）观察到的免疫反应类型，d） 防止tick传递的同源和异源挑战的保护。我们相信这个项目， 在强大的科学前提下，解决了一个重大的公共卫生问题。目标是创新的 因为我们将是第一个使用生理上相关的动物研究RMSF疫苗开发的组 tick病原体感染模型。我们应用的中心假设是WCA预防致命 由血液和壁虱传播引起的RMSF，由地理远处的病原体菌株引起的RMSF， 刺激免疫保护一年或更长时间。该应用程序的具体目的是：1）评估 在定义疫苗保护时制备WCA和佐剂的灭活方法。 2）评估WCA 防止tick传递的挑战。 3）评估WCA针对R. Rickettsii异源的保护 应变感染挑战。在该项目的结论结束时，我们希望我们的努力将完全转化为 发达的疫苗，该疫苗在已知自然获得R. rickettsii感染的动物模型中有效 从受感染的壁虱导致威胁生命的RMSF。我们相信实现此应用程序的目标将 在不久的将来，扩展疫苗研究以保护人们免受这种致命疾病的侵害。