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寨卡病毒样颗粒在小鼠中诱导产生保护性抗体。

Zika virus like particles elicit protective antibodies in mice.

机构信息

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United States of America.

出版信息

PLoS Negl Trop Dis. 2018 Feb 5;12(2):e0006210. doi: 10.1371/journal.pntd.0006210. eCollection 2018 Feb.

Abstract

Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever. Since its recent emergence in 2014 in the American continent, ZIKV infection during pregnancy has been closely associated with a wide range of congenital abnormalities. To date, no vaccines or antivirals are publicly available. We developed Zika virus-like particles (VLPs) and evaluated their immunogenicity and protective efficacy in mouse models. ZIKV VLPs (ZIKVLPs) formulated with alum were injected into 6-8-week-old interferon deficient AG129 mice as well as wild type BALB/c mice. Control mice received PBS/alum. Animals were challenged with 200 PFU (>1000 AG129 LD50s) of ZIKV strain H/PF/2013. All vaccinated mice survived with no morbidity or weight loss while control animals either died at 9 days post challenge (AG129) or had increased viremia (BALB/c). Neutralizing antibodies were observed in all ZIKVLP vaccinated mice. The role of neutralizing antibodies in protecting mice was demonstrated by passive transfer. Our findings demonstrate the protective efficacy of the ZIKVLP vaccine and highlight the important role that neutralizing antibodies play in protection against ZIKV infection.

摘要

蚊媒传播的 Zika 病毒(ZIKV)通常引起一种轻微且自限性的疾病,称为 Zika 热。自 2014 年在美洲大陆首次出现以来,孕妇 Zika 病毒感染与广泛的先天性异常密切相关。迄今为止,尚无公开的疫苗或抗病毒药物。我们开发了 Zika 病毒样颗粒(VLPs),并在小鼠模型中评估了它们的免疫原性和保护效力。用明矾配制的 Zika 病毒样颗粒(ZIKVLPs)注射到 6-8 周龄干扰素缺陷的 AG129 小鼠以及野生型 BALB/c 小鼠中。对照小鼠接受 PBS/明矾。用 200PFU(>1000 AG129LD50)的 Zika 病毒株 H/PF/2013 对动物进行攻击。所有接种疫苗的小鼠均未出现发病或体重减轻,而对照动物在挑战后 9 天死亡(AG129)或病毒血症增加(BALB/c)。所有接种 ZIKVLP 的小鼠均观察到中和抗体。通过被动转移证明了中和抗体在保护小鼠中的作用。我们的研究结果证明了 ZIKVLP 疫苗的保护效力,并强调了中和抗体在预防 Zika 病毒感染中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caee/5814096/90d051accc2d/pntd.0006210.g001.jpg

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