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以一种已获许可的减毒活黄病毒疫苗为基础开发嵌合寨卡疫苗。

Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

作者信息

Li Xiao-Feng, Dong Hao-Long, Wang Hong-Jiang, Huang Xing-Yao, Qiu Ye-Feng, Ji Xue, Ye Qing, Li Chunfeng, Liu Yang, Deng Yong-Qiang, Jiang Tao, Cheng Gong, Zhang Fu-Chun, Davidson Andrew D, Song Ya-Jun, Shi Pei-Yong, Qin Cheng-Feng

机构信息

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.

Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China.

出版信息

Nat Commun. 2018 Feb 14;9(1):673. doi: 10.1038/s41467-018-02975-w.

DOI:10.1038/s41467-018-02975-w
PMID:29445153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5813210/
Abstract

The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

摘要

寨卡病毒(ZIKV)在全球范围内的传播及其与先天性缺陷的意外关联,使得快速开发一种安全有效的疫苗成为必要。在此,我们报告了一种重组嵌合寨卡病毒候选疫苗(称为ChinZIKV)的研发和特性,该疫苗以已获许可的日本脑炎减毒活疫苗SA14 - 14 - 2作为基因骨架,表达寨卡病毒的prM - E蛋白。ChinZIKV在体外保留其复制活性和遗传稳定性,同时在多种动物模型中表现出减毒表型。值得注意的是,用单剂量ChinZIKV免疫小鼠和恒河猴可引发强烈且持久的免疫反应,并对寨卡病毒攻击提供完全保护。重要的是,用ChinZIKV免疫的雌性小鼠在孕期受到寨卡病毒攻击时可免受胎盘和胎儿损伤。总体而言,我们的研究提供了一个应对寨卡病毒紧急情况的替代疫苗平台,ChinZIKV的安全性、免疫原性和保护特性值得进一步开展临床研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/7e969e89cc0c/41467_2018_2975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/2e4cf6e3b1ff/41467_2018_2975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/3f8690004214/41467_2018_2975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/f45dfe1fe7f6/41467_2018_2975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/e07ce81dc4e9/41467_2018_2975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/7e969e89cc0c/41467_2018_2975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/2e4cf6e3b1ff/41467_2018_2975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/3f8690004214/41467_2018_2975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/f45dfe1fe7f6/41467_2018_2975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/e07ce81dc4e9/41467_2018_2975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8091/5813210/7e969e89cc0c/41467_2018_2975_Fig5_HTML.jpg

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