Preclinical Evaluation of a Live Attenuated Chikungunya Vaccine

Procedia in vaccinology Pub Date : 2012-01-01 DOI:10.1016/j.provac.2012.04.019

Jill A. Livengood , Charalambos D. Partidos , Kenneth Plante , Rob Seymour , Rodion Gorchakov , Laszlo Varga , Joanna Paykel , James Weger , Aurelia Haller , Dan T. Stinchcomb , Jorge Osorio , Scott Weaver

{"title":"Preclinical Evaluation of a Live Attenuated Chikungunya Vaccine","authors":"Jill A. Livengood , Charalambos D. Partidos , Kenneth Plante , Rob Seymour , Rodion Gorchakov , Laszlo Varga , Joanna Paykel , James Weger , Aurelia Haller , Dan T. Stinchcomb , Jorge Osorio , Scott Weaver","doi":"10.1016/j.provac.2012.04.019","DOIUrl":null,"url":null,"abstract":"<div><p>Recently, Chikungunya virus (CHIKV) re-emerged in Africa and spread in the Indian subcontinent, South East Asia and Italy causing millions of cases of debilitating arthritis and fever in endemic ppulations and in travellers highlighting its growing impact on public health. Currently, there are no licensed vaccines to protect against CHIKV available. We developed a novel live attenuated CHIKV vaccine by using a rational attenuation mechanism that also prevents the infection of mosquito vectors. The subgenomic promoter was inactivated using 13 synonymous mutations and an internal ribosome entry site (IRES) from encephalomyocarditis virus was inserted into a cDNA CHIKV clone to drive translation of the structural protein genes. This new CHIKV vaccine strain was highly stable, safe, immunogenic and protective in mice. Current pre-clinical development efforts are aiming to test this vaccine in non-human primates and complete the Investigational New Drug (IND)-enabling studies necessary to begin human clinical testing.</p></div>","PeriodicalId":89221,"journal":{"name":"Procedia in vaccinology","volume":"6 ","pages":"Pages 141-149"},"PeriodicalIF":0.0000,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.provac.2012.04.019","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Procedia in vaccinology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1877282X12000215","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 1

Abstract

Recently, Chikungunya virus (CHIKV) re-emerged in Africa and spread in the Indian subcontinent, South East Asia and Italy causing millions of cases of debilitating arthritis and fever in endemic ppulations and in travellers highlighting its growing impact on public health. Currently, there are no licensed vaccines to protect against CHIKV available. We developed a novel live attenuated CHIKV vaccine by using a rational attenuation mechanism that also prevents the infection of mosquito vectors. The subgenomic promoter was inactivated using 13 synonymous mutations and an internal ribosome entry site (IRES) from encephalomyocarditis virus was inserted into a cDNA CHIKV clone to drive translation of the structural protein genes. This new CHIKV vaccine strain was highly stable, safe, immunogenic and protective in mice. Current pre-clinical development efforts are aiming to test this vaccine in non-human primates and complete the Investigational New Drug (IND)-enabling studies necessary to begin human clinical testing.

查看原文本刊更多论文

基孔肯雅减毒活疫苗的临床前评价

最近，基孔肯雅病毒(CHIKV)在非洲再次出现，并在印度次大陆、东南亚和意大利传播，在流行人群和旅行者中造成数百万例衰弱性关节炎和发热病例，突出表明其对公共卫生的影响日益严重。目前，还没有获得许可的预防CHIKV的疫苗。我们利用合理的减毒机制研制了一种新型减毒活疫苗，该疫苗还能防止蚊虫媒介的感染。利用13个同义突变使亚基因组启动子失活，并将脑心肌炎病毒的内部核糖体进入位点(IRES)插入cDNA CHIKV克隆中，以驱动结构蛋白基因的翻译。该疫苗株在小鼠体内具有高度稳定性、安全性、免疫原性和保护性。目前临床前开发工作的目标是在非人类灵长类动物中测试这种疫苗，并完成研究性新药(IND)研究，这是开始人体临床试验所必需的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Procedia in vaccinology

自引率

0.00%

发文量