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嵌合黄热病-寨卡病毒疫苗候选物可完全保护小鼠免受黄热病病毒感染。

A chimeric yellow fever-Zika virus vaccine candidate fully protects against yellow fever virus infection in mice.

机构信息

KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, Laboratory of Virology and Chemotherapy, Leuven, Belgium.

出版信息

Emerg Microbes Infect. 2020 Mar 2;9(1):520-533. doi: 10.1080/22221751.2020.1730709. eCollection 2020.

DOI:10.1080/22221751.2020.1730709
PMID:32116148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7067203/
Abstract

The recent Zika virus (ZIKV) epidemic in the Americas, followed by the yellow fever virus (YFV) outbreaks in Angola and Brazil highlight the urgent need for safe and efficient vaccines against the ZIKV as well as much greater production capacity for the YFV-17D vaccine. Given that the ZIKV and the YFV are largely prevalent in the same geographical areas, vaccines that would provide dual protection against both pathogens may obviously offer a significant benefit. We have recently engineered a chimeric vaccine candidate (YF-ZIKprM/E) by swapping the sequences encoding the YFV-17D surface glycoproteins prM/E by the corresponding sequences of the ZIKV. A single vaccine dose of YF-ZIKprM/E conferred complete protection against a lethal challenge with wild-type ZIKV strains. Surprisingly, this vaccine candidate also efficiently protected against lethal YFV challenge in various mouse models. We demonstrate that CD8 but not CD4 T cells, nor ZIKV neutralizing antibodies are required to confer protection against YFV. The chimeric YF-ZIKprM/E vaccine may thus be considered as a dual vaccine candidate efficiently protecting mice against both the ZIKV and the YFV, and this following a single dose immunization. Our finding may be particularly important in the rational design of vaccination strategies against flaviviruses, in particular in areas where YFV and ZIKV co-circulate.

摘要

最近美洲的寨卡病毒(ZIKV)疫情,以及随后安哥拉和巴西的黄热病病毒(YFV)爆发,突显了迫切需要针对 ZIKV 的安全有效的疫苗,以及对 YFV-17D 疫苗的更大生产能力。鉴于 ZIKV 和 YFV 主要在相同的地理区域流行,针对这两种病原体的双重保护疫苗显然会带来显著的益处。我们最近通过交换 YFV-17D 表面糖蛋白 prM/E 的序列,用 ZIKV 的相应序列,设计了一种嵌合疫苗候选物(YF-ZIKprM/E)。YF-ZIKprM/E 的单次疫苗剂量可完全预防野生型 ZIKV 株的致死性挑战。令人惊讶的是,这种疫苗候选物在各种小鼠模型中也能有效地预防致死性 YFV 挑战。我们证明 CD8 而不是 CD4 T 细胞,也不需要中和 ZIKV 的抗体来提供针对 YFV 的保护。嵌合的 YF-ZIKprM/E 疫苗因此可以被认为是一种双重疫苗候选物,能够有效地保护小鼠免受 ZIKV 和 YFV 的侵害,而且只需单次免疫接种。我们的发现对于黄病毒的疫苗接种策略的合理设计可能特别重要,特别是在 YFV 和 ZIKV 同时流行的地区。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/7e4e3a14a165/TEMI_A_1730709_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/ca3300ead7eb/TEMI_A_1730709_F0001_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/3cc4cc0c717f/TEMI_A_1730709_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/8493dbbf1920/TEMI_A_1730709_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/e6ab9f186734/TEMI_A_1730709_F0005_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/c5def15bd27c/TEMI_A_1730709_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/7e4e3a14a165/TEMI_A_1730709_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/ca3300ead7eb/TEMI_A_1730709_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/3d4cb6fea989/TEMI_A_1730709_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/3cc4cc0c717f/TEMI_A_1730709_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/8493dbbf1920/TEMI_A_1730709_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/e6ab9f186734/TEMI_A_1730709_F0005_OB.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/c5def15bd27c/TEMI_A_1730709_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f868/7067203/7e4e3a14a165/TEMI_A_1730709_F0007_OC.jpg

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