Chikungunya Recombinant Subunit Vaccine

基孔肯雅热重组亚单位疫苗

• 批准号: 9321278
• 负责人: DAVID E CLEMENTS
• 金额: $ 30万
• 依托单位: HAWAII BIOTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-22 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321278
• 关键词: Acute; Adjuvant; Aedes; Africa; Alphavirus; Aluminum; Americas; Antibody Response; Antigens; Area; Arthralgia; Asia; Attenuated; Biochemical; Biotechnology; Blood; Categories; Cells; Chikungunya virus; Collaborations; Country; Culicidae; Data; Dengue Virus; Development; Disease; Disease Outbreaks; Dose; Economics; Epidemic; Epitopes; Exanthema; Fever; Formulation; GPI-0100; Geography; Glycoproteins; Goals; Hawaii; Headache; Human; Human Resources; Immune response; Immunization; Immunize; Inbred BALB C Mice; Indian Ocean; Infection; Insecta; Intervention; Island; Latin American; Measures; Medicine; Military Personnel; Monoclonal Antibodies; Morbidity - disease rate; Mus; Outcome; Phase I Clinical Trials; Photophobia; Population; Preventive vaccine; Production; Protein Subunits; Proteins; Recombinant Proteins; Recombinant Vaccines; Recombinants; Reporting; Research; Risk; Safety; Saponins; Serum; South American; Subunit Vaccines; Supportive care; System; Technology; Testing; Therapeutic; Tissues; Vaccines; Virus; Virus Diseases; Virus-like particle; West Indies; West Nile virus; World Health Organization; base; cell mediated immune response; chikungunya; college; env Gene Products; immunogenic; immunogenicity; mouse model; neutralizing antibody; pathogen; preclinical study; prevent; protective efficacy; protein structure; public health relevance; recombinant virus; transmission process; vaccine candidate; vaccine development; vector mosquito; virus envelope

 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.

 描述（由应用程序提供）：Chikungunya病毒（CHIKV）是一种α病毒，被分类为C类优先病原体，会导致人类发烧，皮疹和关节痛。在过去的十年中，Chikv爆发已经超越了非洲和亚洲的地方性地区，首先是印度洋的岛屿，以及最近到美洲。世界卫生组织报道说，截至2014年10月，在加勒比群岛，拉丁美洲国家和一些南美国家中，已记录了超过776,000例可疑奇京尼亚病例。由于其范围的地理扩展及其人类病例数量的增加，因此CHIKV被认为是一种重新出现的病原体。促成这种重新出现的一个因素是艾德斯白化蚊子传播的病毒适应。目前，尚无授权疫苗或治疗来防止CHIKV感染。与许多病毒感染一样，支持治疗是唯一可用的治疗方法。鉴于Chikv引起的严重发病率，其迅速的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，以减少由这种疾病造成的燃烧。该应用是针对Chikv重组亚基疫苗的开发。正在开发多种平台技术，包括灭活病毒，活衰减的病毒，嵌合实时衰减病毒，病毒样粒子和亚基。与所有疫苗一样，在需要BSL-3处理的CHIKV等优先病原体中，制造中的安全性和经济性的结合至关重要。拟议的重组亚基方法提供了一种提供安全稳定的制造平台的方法，并允许对剂量进行调整，以便引发强大的免疫响应，从而为CHIKV感染提供了强有力的保护。为了实现这一目标，将评估重组亚基蛋白的重组亚基蛋白，这些蛋白将评估带有CHIKV包膜糖蛋白的相关表位的特定域。该项目的具体目的是：1）产生重组CHIKV E2亚基蛋白2）在小鼠中表现出候选疫苗的免疫原性； 3）证明将根据维持天然蛋白质结构的组合物选择候选疫苗，并引起相关且可靠的免疫反应，该反应能够预防CHIKV挑战后的疾病。已经建立了夏威夷生物技术与贝勒医学院之间的合作，以开发和评估成功的CHIKV疫苗。 CHIKV重组亚基疫苗的发展对于减缓这种重新出现的C类病毒的传播并防止CHIKV感染引起的严重发病率将具有很大的价值。