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Cross-protective efficacies of highly-pathogenic avian influenza H5N1 vaccines against a recent H5N8 virus

机译:高致病性禽流感H5N1疫苗对最近的H5N8病毒的交叉保护作用

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摘要

To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)]. Although relatively low cross-reactivities (10-40 HI titer) were observed against heterologous H5N8 virus, immunized animals were 100% protected from challenge with the 20 mLD(50) of H5N8 virus, with the exception of mice vaccinated with 3.5 mu g of Rg Vietnam/1194/04xPR8. Of note, the Rg Korea/ES223N/03xPR8 vaccine provided not only effective protection, but also markedly inhibited viral replication in the lungs and nasal swabs of vaccine recipients within five days of HPAI H5N8 virus challenge. Further, we demonstrated that antibody-dependent cell-mediated cytotoxicity (ADCC) of an antibody-coated target cell by cytotoxic effector cells also plays a role in the heterologous protection of H5N1 vaccines against H5N8 challenge. (C) 2016 Elsevier Inc. All rights reserved.
机译:为了研究高致病性禽流感H5N1病毒对最近的HPAI H5N8病毒的交叉保护疫苗功效,我们用通过逆向遗传学(Rg)开发的三种明矾佐剂灭活的完整H5N1疫苗免疫了C57BL / 6小鼠和雪貂:[越南/ 1194 / 04xPR8(第1类),Korea / W149 / 06xPR8(第2.2类)和Korea / ES223N / 03xPR8(第2.5类)]]。尽管针对异源H5N8病毒观察到相对较低的交叉反应性(10-40 HI效价),但用20 mLD(50)H5N8病毒100%保护了免疫动物免受攻击,但接种了3.5μgH5N8疫苗的小鼠除外越南Rg / 1194 / 04xPR8。值得注意的是,Rg Korea / ES223N / 03xPR8疫苗不仅提供了有效的保护,而且还显着抑制了HPAI H5N8病毒攻击后五天内疫苗接种者肺和鼻拭子中的病毒复制。此外,我们证明了细胞毒性效应细胞对抗体包被的靶细胞的抗体依赖性细胞介导的细胞毒性(ADCC)在H5N1疫苗针对H5N8攻击的异源保护中也发挥着作用。 (C)2016 Elsevier Inc.保留所有权利。

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