Chikungunya Recombinant Subunit Vaccine

基孔肯雅热重组亚单位疫苗

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：基孔肯雅病毒（CHIKV）是一种甲病毒，被列为 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 疫情已蔓延至非洲和亚洲流行地区以外。，首先是印度洋岛屿，最近是美洲。世界卫生组织报告称，截至 2014 年 10 月，已有超过 776,000 例疑似病例。由于其范围的地理扩张和人类病例数量的增加，基孔肯雅热病毒被认为是一种重新出现的病原体；导致这种病毒再次出现的因素是病毒适应了白纹伊蚊的传播，目前没有获得许可的疫苗或治疗方法可以预防 CHIKV 感染，与许多病毒感染一样，支持治疗是唯一可用的。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这种疾病造成的负担。本申请旨在开发 CHIKV 重组体。亚单位疫苗。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、嵌合减毒活病毒、病毒样颗粒和亚单位。疫苗，特别是对于需要 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至关重要。所提出的重组亚基方法提供了一种提供安全稳定的生产平台并允许生产的方法。轻松调整剂量以引发强大的免疫反应，提供针对 CHIKV 感染的强大保护为了实现这一目标，重组亚基蛋白专注于具有 CHIKV 包膜糖蛋白相关表位的特定结构域。该项目的具体目标是：1) 生产重组 CHIKV E2 亚基蛋白；2) 证明候选疫苗在小鼠中的免疫原性；以及 3) 证明候选疫苗在小鼠中的保护功效。亚基蛋白将在已建立的稳定昆虫表达系统中生产，该系统现已提交多个 IND 申请，将根据保持天然蛋白结构并引发的组合物来选择候选疫苗。夏威夷生物技术公司和贝勒医学院之间已经建立了能够预防 CHIKV 攻击后疾病的相关且强大的免疫反应，以开发和评估成功的 CHIKV 疫苗。CHIKV 重组亚单位疫苗的开发将具有巨大的价值。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。