Chikungunya vaccine candidate developed by codon pair de-optimization

摘要 基孔肯雅病毒（CHIKV）是披膜病毒科中的甲病毒，是一种重要的且 近年来在世界各地传播的危险病毒病原体。CHIKV病因 基孔肯雅热和严重的关节痛，可能持续数月。比如登革热病毒 除了登革病毒（DENV）之外，CHIKV也是节肢动物传播的病毒（虫媒病毒）。目前，没有获得许可的疫苗或 这种药物可用于人类治疗基孔肯雅病毒。 我们最近开发了一种基于理性的计算机辅助基因的新技术， 设计，称为合成减毒病毒工程（SAVE），以减毒加和减毒 链RNA病毒（脊髓灰质炎病毒、流感病毒、登革热病毒）， 引入不利密码子对。这些密码子对去优化的病毒都成功地 在组织培养和动物模型中均减毒。在这里，我们建议延长SAVE 这种新出现的危险的病毒病原体基孔肯雅病毒的方法， 分离减毒病毒株。在计算机的帮助下， 我们将重新编码CHIKV的基因组，使其包含大片段 （编码蛋白nsP4，E2，E1）的密码子对在哺乳动物中不受欢迎。基于 我们先前的研究预期这些重新编码的CHIK病毒将被类似地减毒， 将作为可能的活疫苗候选者

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