Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71

IF 5.5 3区医学 Q1 Medicine

Virologica Sinica Pub Date : 2024-10-01 DOI:10.1016/j.virs.2024.09.008

Rong-Rong Zhang , Meng-Jiao He , Chao Zhou , Yan-Peng Xu , Wei Tang , Tian-Shu Cao , Zheng-Jian Wang , Mei Wu , Tao Ming , Yi-Jiao Huang , Meng-Xu Sun , Hui Zhao , Yong-Qiang Deng , Xiao-Feng Li , Bin Wang , Qing Ye , Cheng-Feng Qin

{"title":"Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71","authors":"Rong-Rong Zhang , Meng-Jiao He , Chao Zhou , Yan-Peng Xu , Wei Tang , Tian-Shu Cao , Zheng-Jian Wang , Mei Wu , Tao Ming , Yi-Jiao Huang , Meng-Xu Sun , Hui Zhao , Yong-Qiang Deng , Xiao-Feng Li , Bin Wang , Qing Ye , Cheng-Feng Qin","doi":"10.1016/j.virs.2024.09.008","DOIUrl":null,"url":null,"abstract":"<div><div>Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. <em>In vitro</em> and <em>in vivo</em> transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR<sup>−/−</sup> mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":null,"pages":null},"PeriodicalIF":5.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virologica Sinica","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1995820X24001470","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR^−/− mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.

查看原文本刊更多论文

合理设计 DNA 发射的人类肠道病毒 71 型减毒活疫苗。

人类肠道病毒 71 型（EV71）已成为影响全球的手足口病（HFMD）的主要致病因子之一。尽管灭活疫苗已获得许可，但基于先进技术平台的其他候选疫苗仍在开发中。在本报告中，我们在特定启动子的控制下合理设计并构建了两种 DNA 发射的减毒活疫苗候选株（pDL-EV71）。由 CMV 启动子驱动的 pDL-EV71 在体外和体内转染成功地产生了具有完全感染性的 EV71。更重要的是，在新生小鼠和 IFNα/βR-/- 小鼠颅内或肌肉注射 pDL-EV71 后，不会引起临床症状，这证明了其安全性。此外，pDL-EV71 的单剂量或双剂量免疫可在小鼠体内激发针对 EV71 的强效中和抗体以及抗原特异性细胞反应。单剂量免疫 10 μg pDL-EV71 可完全保护免疫母鼠所生的新生儿免受致死性 EV71 感染。总之，我们目前的研究结果表明，pDL-EV71 是一种安全有效的 EV71 候选疫苗，可供进一步开发。

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

Virologica Sinica Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

7.70

自引率

1.80%

发文量

3149

期刊介绍： Virologica Sinica is an international journal which aims at presenting the cutting-edge research on viruses all over the world. The journal publishes peer-reviewed original research articles, reviews, and letters to the editor, to encompass the latest developments in all branches of virology, including research on animal, plant and microbe viruses. The journal welcomes articles on virus discovery and characterization, viral epidemiology, viral pathogenesis, virus-host interaction, vaccine development, antiviral agents and therapies, and virus related bio-techniques. Virologica Sinica, the official journal of Chinese Society for Microbiology, will serve as a platform for the communication and exchange of academic information and ideas in an international context. Electronic ISSN: 1995-820X; Print ISSN: 1674-0769