Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents.

Jason S Richardson, Gary Wong, Stéphane Pillet, Samantha Schindle, Jane Ennis, Jeffrey Turner, James E Strong, Gary P Kobinger
{"title":"Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents.","authors":"Jason S Richardson,&nbsp;Gary Wong,&nbsp;Stéphane Pillet,&nbsp;Samantha Schindle,&nbsp;Jane Ennis,&nbsp;Jeffrey Turner,&nbsp;James E Strong,&nbsp;Gary P Kobinger","doi":"10.4172/2157-2526.s1-007","DOIUrl":null,"url":null,"abstract":"<p><p>Zaire Ebola virus (ZEBOV) is a pathogen that causes severe hemorrhagic fever in humans and non-human primates. There are currently no licensed vaccines or approved treatments available against ZEBOV infections. The goal of this work was to evaluate different treatment strategies in conjunction with a replication deficient, recombinant human adenovirus serotype 5-based vaccine expressing the Zaire Ebola virus glycoprotein (Ad-CAGoptZGP) in Ebola infected mice and guinea pigs.Guinea pigs were treated with Ad-CAGoptZGP in combination with different treatment strategies after challenge with guinea pig adapted-ZEBOV (GA-ZEBOV). B10.BR mice were used to further characterize efficacy and immune responses following co-administration of Ad-CAGoptZGP with the most effective treatment: AdHu5 expressing recombinant IFN-α (hereafter termed DEF201) after challenge with a lethal dose of mouse adapted-ZEBOV (MA-ZEBOV).In mice, DEF201 treatment was able to elicit full protection against a lethal dose of MA-ZEBOV when administered 30 minutes after infection. In guinea pigs the Ad-CAGoptZGP and DEF201 combination therapy elicited full protection when treated 30 minutes post-exposure and were a superior treatment to Ad-CAGoptZGP supplemented with recombinant IFN-α protein. Further analysis of the immune response revealed that addition of DEF201 to Ad-CAGoptZGP enhances the resulting adaptive immune response against ZGP. The results highlight the importance of the innate immune response in the prevention of ZEBOV pathogenesis and support further development of the Ad-CAGoptZGP with DEF201 treatment combination for post-exposure therapy against ZEBOV infection.</p>","PeriodicalId":73625,"journal":{"name":"Journal of bioterrorism & biodefense","volume":" S1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2011-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509938/pdf/nihms-408720.pdf","citationCount":"29","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of bioterrorism & biodefense","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.4172/2157-2526.s1-007","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 29

Abstract

Zaire Ebola virus (ZEBOV) is a pathogen that causes severe hemorrhagic fever in humans and non-human primates. There are currently no licensed vaccines or approved treatments available against ZEBOV infections. The goal of this work was to evaluate different treatment strategies in conjunction with a replication deficient, recombinant human adenovirus serotype 5-based vaccine expressing the Zaire Ebola virus glycoprotein (Ad-CAGoptZGP) in Ebola infected mice and guinea pigs.Guinea pigs were treated with Ad-CAGoptZGP in combination with different treatment strategies after challenge with guinea pig adapted-ZEBOV (GA-ZEBOV). B10.BR mice were used to further characterize efficacy and immune responses following co-administration of Ad-CAGoptZGP with the most effective treatment: AdHu5 expressing recombinant IFN-α (hereafter termed DEF201) after challenge with a lethal dose of mouse adapted-ZEBOV (MA-ZEBOV).In mice, DEF201 treatment was able to elicit full protection against a lethal dose of MA-ZEBOV when administered 30 minutes after infection. In guinea pigs the Ad-CAGoptZGP and DEF201 combination therapy elicited full protection when treated 30 minutes post-exposure and were a superior treatment to Ad-CAGoptZGP supplemented with recombinant IFN-α protein. Further analysis of the immune response revealed that addition of DEF201 to Ad-CAGoptZGP enhances the resulting adaptive immune response against ZGP. The results highlight the importance of the innate immune response in the prevention of ZEBOV pathogenesis and support further development of the Ad-CAGoptZGP with DEF201 treatment combination for post-exposure therapy against ZEBOV infection.

啮齿类动物埃博拉病毒感染暴露后不同治疗策略的评价
扎伊尔埃博拉病毒(ZEBOV)是一种在人类和非人类灵长类动物中引起严重出血热的病原体。目前还没有针对ZEBOV感染的许可疫苗或批准的治疗方法。这项工作的目的是在埃博拉感染小鼠和豚鼠中评估不同的治疗策略,并结合表达扎伊尔埃博拉病毒糖蛋白(Ad-CAGoptZGP)的复制缺陷重组人腺病毒血清5型疫苗。用豚鼠适应的zebov (GA-ZEBOV)攻毒后,将Ad-CAGoptZGP与不同的处理策略结合处理。B10。用BR小鼠进一步表征Ad-CAGoptZGP与表达重组IFN-α的AdHu5(以下称为DEF201)在用致死剂量的小鼠适应zebov (MA-ZEBOV)攻毒后的疗效和免疫应答。在小鼠中,在感染后30分钟给予DEF201治疗能够引起对致死剂量MA-ZEBOV的充分保护。在豚鼠中,Ad-CAGoptZGP和DEF201联合治疗在暴露后30分钟可以获得充分的保护,并且优于Ad-CAGoptZGP补充重组IFN-α蛋白的治疗。进一步的免疫应答分析表明,在Ad-CAGoptZGP中添加DEF201增强了对ZGP的适应性免疫应答。这些结果强调了先天免疫反应在预防ZEBOV发病机制中的重要性,并支持进一步开发Ad-CAGoptZGP与DEF201联合治疗ZEBOV感染的暴露后治疗。
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
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信