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日本脑炎病毒/黄热病病毒嵌合体安全,并能在脑内 challenged 小鼠中提供针对黄热病病毒的完全保护。

Japanese encephalitis virus/yellow fever virus chimera is safe and confers full protection against yellow fever virus in intracerebrally challenged mice.

机构信息

Department of Viral Vaccines, Chengdu Institute of Biological Products Co., Ltd, China National Biotech Group, Chengdu 610023, PR China.

Department of Arbovirus Vaccines, National Institutes for Food and Drug Control, Beijing 100050, PR China.

出版信息

Vaccine. 2018 Apr 25;36(18):2450-2455. doi: 10.1016/j.vaccine.2018.03.038. Epub 2018 Mar 23.

Abstract

Yellow fever (YF) is an acute viral haemorrhagic disease caused by the yellow fever virus (YFV), which remains a potential threat to public health. The live-attenuated YF vaccine (17D strain) is a safe and highly effective measure against YF. However, increasing adverse events have been associated with YF vaccinations in recent years; thus, safer, alternative vaccines are needed. In this study, using the Japanese encephalitis live vaccine strain SA14-14-2 as a backbone, a novel chimeric virus was constructed by replacing the pre-membrane (prM) and envelope (E) genes with their YFV 17D counterparts.The chimeric virus exhibited a reduced growth rate and a much smaller plaque morphology than did either parental virus. Furthermore, the chimera was much less neurovirulent than was YF17D and protected mice that were challenged with a lethal dose of the YF virus. These results suggest that this chimera has potential as a novel attenuated YF vaccine.

摘要

黄热病(YF)是一种由黄热病毒(YFV)引起的急性病毒性出血性疾病,仍然对公共卫生构成潜在威胁。减毒活黄热病疫苗(17D 株)是预防黄热病的安全有效措施。然而,近年来与黄热病疫苗接种相关的不良反应事件不断增加;因此,需要更安全的替代疫苗。在这项研究中,使用日本脑炎活疫苗株 SA14-14-2 作为骨架,通过用其 YFV 17D 对应物替换前膜(prM)和包膜(E)基因,构建了一种新型嵌合病毒。与任何亲本病毒相比,嵌合病毒的生长速度较慢,斑块形态较小。此外,嵌合体的神经毒力比 YF17D 低得多,并保护了接受致死剂量黄热病毒攻击的小鼠。这些结果表明,这种嵌合体具有作为新型减毒黄热病疫苗的潜力。

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