Chikungunya vaccine candidate developed by codon pair de-optimization

通过密码子对去优化开发的基孔肯雅候选疫苗

基本信息

批准号：
9296049
负责人：
Yutong Song
金额：
$ 23.84万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
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：
2016-06-14 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9296049
关键词：
Aedes Affect African Algorithms Alphavirus Americas Analgesics Animal Model Antibodies Arboviruses Area Arthralgia Attenuated Attenuated Vaccines Breathing Caribbean region Cell Line Centers for Disease Control and Prevention (U.S.)Central America Chikungunya virus Clinical Codon Nucleotides Computer Assisted Computers Country Culicidae Dangerousness Data Dengue Dengue Virus Diagnosis Disease Disease Outbreaks Engineering Epidemic European Exanthema Exposure to Family Fetus Fever Frequencies Genes Genome Human Human Bites Human poliovirus India Indian Ocean Islands Individual Indonesia Infection Island Laboratories Language Lead Malaysia Mammals Medicine Mothers Mus Myalgia Names Nausea Non-Steroidal Anti-Inflammatory Agents Pain Pharmaceutical Preparations Pharmacotherapy Proteins RNA RNA Viruses Risk Scientist Singapore South America Southeastern Asia Symptoms Tanganyika Tanzania Thailand Time Togaviridae United States United States National Institutes of Health Vaccines Variant Viral Virus Virus Diseases Walking adaptive immune response aerosolized attenuation base chikungunya design design and construction influenzavirus new technology nonhuman primate novel pathogen prevent southeast Asian suckling tissue culture vaccine candidate

项目摘要

Abstract Chikungunya virus (CHIKV), an alphavirus in the Togaviridae family, is an important and dangerous viral pathogen that has spread around the world in recent years. CHIKV causes chikungunya fever and severe arthralgia that may persist for several months. Like Dengue Virus (DENV), CHIKV is also an arthropod-borne virus (arbovirus). Currently, no licensed vaccine or drug is available for human use for Chikungunya virus. We have recently developed a novel technology that is based on rational, computer-aided gene design, termed Synthetic Attenuated Virus Engineering (SAVE), to attenuate plus and minus strand RNA viruses (poliovirus, influenza virus dengue virus) by recoding their their genomes to introduce unfavored codon pairs. Those codon pair deoptimized viruses were all successfully attenuated both in tissue culture and in an animal model. Here, we propose to extend the SAVE approach to this emerging and dangerous viral pathogen, Chikungunya virus, to pursue the isolation of an attenuated viral strain. With the aid of computers and specifically tailored algorithms we will recode the genome of CHIKV such that it will contain large segments (encoding either the proteins nsP4, E2, E1) of codon pairs dis-favored in mammals. Based on our previous studies we expect that these recoded CHIK viruses will be similarly attenuated and will serve as possible live vaccine candidates

抽象的基孔肯雅病毒（CHIKV）是披膜病毒科中的一种甲病毒，是一种重要且重要的病毒。近年来在世界各地传播的危险病毒病原体。 CHIKV 病因基孔肯雅热和严重关节痛可能持续数月。就像登革热病毒一样 (DENV)，CHIKV 也是一种节肢动物传播的病毒（虫媒病毒）。目前尚无获得许可的疫苗或该药物可供人类用于治疗基孔肯雅病毒。我们最近开发了一种基于理性、计算机辅助基因的新技术设计，称为合成减毒病毒工程（SAVE），以减弱正负病毒链RNA病毒（脊髓灰质炎病毒、流感病毒、登革热病毒）通过将其基因组重新编码为引入不利的密码子对。这些密码子对去优化病毒均成功在组织培养和动物模型中均减弱。在此，我们建议延长 SAVE 方法来应对这种新兴的危险病毒病原体基孔肯雅病毒，以追求减毒病毒株的分离。借助计算机和专门定制的我们将通过算法重新编码 CHIKV 的基因组，使其包含大片段（编码蛋白质 nsP4、E2、E1）在哺乳动物中不受青睐的密码子对。基于我们之前的研究预计这些重新编码的 CHIK 病毒也会得到类似的减毒并且将作为可能的活疫苗候选者