Chikungunya Recombinant Subunit Vaccine

 描述(申请人提供)：基孔肯雅病毒(CHIKV)是一种甲型病毒，被归类为C类优先病原体，可引起人类发烧、皮疹和关节痛。在过去十年中，CHIKV疫情已经蔓延到非洲和亚洲的流行地区以外，首先蔓延到印度洋的岛屿，最近蔓延到美洲。世界卫生组织报告称，截至2014年10月，加勒比海岛屿、拉丁美洲国家和一些南美国家记录的基孔肯雅热疑似病例超过77.6万例。由于其地域范围的扩大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；导致这种重新出现的一个促成因素是适应白纹伊蚊传播的病毒。目前，还没有获得许可的疫苗或治疗药物来预防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，预防性疫苗将提供一种有效的手段来减轻该疾病造成的负担。本申请是针对CHIKV重组亚单位疫苗的开发。有几种候选疫苗正在开发中，使用各种平台技术，包括灭活病毒、减毒活病毒、嵌合减毒病毒、病毒样颗粒和亚单位。与所有疫苗一样，尤其是需要BSL-3处理的CHIKV等优先病原体，生产中的安全性和经济性的结合是至关重要的。建议的重组亚单位方法提供了一种方法，提供了一个安全和稳定的制造平台，并允许容易地调整剂量，以引起强大的免疫反应，提供对CHIKV感染的强大保护。为了实现这一目标，将评估具有CHIKV包膜糖蛋白相关表位的特定结构域的重组亚单位蛋白。该项目的具体目标是：1)生产重组CHIKV E2亚单位蛋白；2)展示候选疫苗在小鼠中的免疫原性；3)展示候选疫苗在小鼠中的保护效果。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生产，目前已有多个IND申请。候选疫苗的选择将基于一种成分，该成分保持天然的蛋白质结构，并引起相关和强大的免疫反应，能够预防CHIKV挑战后的疾病。夏威夷生物技术公司和贝勒医学院已经建立了合作关系，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于减缓这种重新出现的C类病毒的传播，预防由CHIKV感染引起的严重发病率具有重要的价值。

 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.