Chikungunya Recombinant Subunit Vaccine

 描述（由申请方提供）：基孔肯雅病毒（CHIKV）是一种甲病毒属，被归类为C类优先病原体，可引起人类发热、皮疹和关节痛。在过去的十年中，CHIKV疫情已经蔓延到非洲和亚洲的流行地区之外，首先是印度洋的岛屿，最近是美洲。世界卫生组织报告说，截至2014年10月，在加勒比岛屿、拉丁美洲国家和一些南美洲国家记录了776，000多例基孔肯雅病疑似病例。由于其范围的这种地理扩展和人类病例数量的增加，CHIKV被认为是一种重新出现的病原体;这种重新出现的一个促成因素是病毒适应白纹伊蚊传播。目前，没有许可的疫苗或治疗剂来保护免受CHIKV感染。与许多病毒感染一样，支持性护理是唯一可用的治疗方法。鉴于CHIKV引起的严重发病率，其迅速出现，以及缺乏任何有针对性的干预措施，预防性疫苗将提供有效的手段来减少这种疾病造成的负担。本申请涉及CHIKV重组亚单位疫苗的开发。有几种候选疫苗正在使用各种平台技术开发中，包括灭活病毒、减毒活病毒、嵌合减毒活病毒、病毒样颗粒和亚基。与所有疫苗一样，特别是对于需要BSL-3处理的优先病原体如CHIKV，生产中安全性和经济性的结合至关重要。所提出的重组亚基方法提供了一种递送安全和稳定的制造平台的手段，并且允许容易地调整剂量，以引发稳健的免疫应答，从而提供针对CHIKV感染的强保护。为了实现这一目标，将评价集中于具有来自CHIKV包膜糖蛋白的相关表位的特定结构域的重组亚基蛋白。本项目的具体目的是：1）生产重组CHIKV E2亚单位蛋白; 2）在小鼠中证明候选疫苗的免疫原性; 3）在小鼠中证明候选疫苗的保护效力。为了实现这些目标，重组E亚基蛋白将在已建立的稳定的昆虫表达系统中产生，现已提交了多个IND申请。候选疫苗将基于保持天然样蛋白质结构的组合物来选择，并且其激发能够在CHIKV攻击后预防疾病的相关和稳健的免疫应答。夏威夷生物技术公司和贝勒医学院已经建立了合作，以开发和评估一种成功的CHIKV疫苗。CHIKV重组亚单位疫苗的研制对减缓CHIKV C类病毒的传播和预防CHIKV感染引起的严重发病具有重要价值。

 DESCRIPTION (provided by applicant): Chikungunya virus (CHIKV) is an alphavirus classified as a category C priority pathogen that causes fever, rash, and arthralgia in humans. In the past decade, CHIKV outbreaks have spread beyond the endemic regions of Africa and Asia, first to the islands in the Indian Ocean, and most recently to the Americas. The World Health Organization has reported that as of October 2014, over 776,000 suspected cases of Chikungunya have been recorded in the Caribbean islands, Latin American countries and some South American countries. Due to this geographic expansion of its range and the increase in the number of human cases, CHIKV is considered to be a re-emerging pathogen; a contributing factor to this re-emergence is the virus adapting to transmission by Aedes albopictus mosquitoes. Currently, there are no licensed vaccines or therapeutics to protect against infection with CHIKV. As with many viral infections, supportive care is the only available treatment. Given the severe morbidity caused by CHIKV, its swift emergence, and the lack of any targeted interventions, a preventative vaccine would provide an effective means to reduce the burden caused by this disease. This application is directed at the development of a CHIKV recombinant subunit vaccine. There are several candidate vaccines under development using a variety of platform technologies including inactivated viruses, live-attenuated viruses, chimeric live-attenuated viruses, virus- like-particles and subunits. As with all vaccines, and in particula for priority pathogens such as CHIKV which requires BSL-3 handling, a combination of safety and economics in manufacturing are of paramount importance. The proposed recombinant subunit approach provides a means to deliver a safe and stable manufacturing platform and allow for easy adjustment of dosing in order to elicit a robust immune response providing strong protection against CHIKV infection. To accomplish this goal, recombinant subunit proteins focused on specific domains with relevant epitopes from the CHIKV envelope glycoproteins will be evaluated. The Specific Aims of this project are: 1) produce recombinant CHIKV E2 subunit proteins 2) demonstrate immunogenicity of candidate vaccines in mice; and 3) demonstrate protective efficacy of candidate vaccines in mice. To achieve these goals, the recombinant E subunit proteins will be produced in an established stable insect expression system for which multiple IND applications have now been filed. A candidate vaccine will be selected on the basis of a composition that maintains native-like protein structure, and which elicits a relevant and robust immune response that is capable of preventing disease following CHIKV challenge. A collaboration between Hawaii Biotech and Baylor College of Medicine has been established to develop and evaluate a successful a CHIKV vaccine. The development of CHIKV recombinant subunit vaccine would be of great value in slowing the spread of this re-emerging Category C virus and preventing the severe morbidity caused by CHIKV infection.