A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades
A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades
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DOI：
10.1038/s41541-019-0155-z
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发表时间：
2020-01-10
期刊：
影响因子：
9.2
通讯作者：
Marzi, Andrea
中科院分区：
文献类型：
--
作者：
Furuyama, Wakako;Reynolds, Pierce;Marzi, Andrea
1997年爆发的禽流感病毒突出了高致病性H5 N1病毒在人类中造成严重疾病的潜力。因此，需要针对H5 N1病毒的有效疫苗来应对全球大流行的潜在威胁。我们之前已经使用水泡性口炎病毒（VSV）平台开发了一种针对埃博拉病毒（EBOV）的快速有效疫苗。在这项研究中，我们产生了重组VSV为基础的H5 N1流感病毒载体，以证明该平台的快速作用泛H5流感病毒疫苗的可行性。我们选择了关于抗原设计和基因组定位的多种方法来定义更优化的疫苗方法。在回收基于VSV的H5 N1流感病毒构建体并在体外表征之后，通过单剂量或初免/加强方案接种小鼠，然后用致死剂量的同源H5进化枝1病毒攻击。我们发现，表达全长血凝素（HAf 1）的VSV载体的单次剂量足以提供100%保护。疫苗载体是快速作用的，如通过在致死性攻击前3天施用时的均匀保护所证明的。此外，单次疫苗接种诱导交叉保护性H5特异性抗体并保护小鼠免受各种H5进化枝2病毒的致死性攻击，突出了基于VSV的HAfl作为泛H5流感病毒应急疫苗的潜力。
The avian influenza virus outbreak in 1997 highlighted the potential of the highly pathogenic H5N1 virus to cause severe disease in humans. Therefore, effective vaccines against H5N1 viruses are needed to counter the potential threat of a global pandemic. We have previously developed a fast-acting and efficacious vaccine against Ebola virus (EBOV) using the vesicular stomatitis virus (VSV) platform. In this study, we generated recombinant VSV-based H5N1 influenza virus vectors to demonstrate the feasibility of this platform for a fast-acting pan-H5 influenza virus vaccine. We chose multiple approaches regarding antigen design and genome location to define a more optimized vaccine approach. After the VSV-based H5N1 influenza virus constructs were recovered and characterized in vitro, mice were vaccinated by a single dose or prime/boost regimen followed by challenge with a lethal dose of the homologous H5 clade 1 virus. We found that a single dose of VSV vectors expressing full-length hemagglutinin (HAfl) were sufficient to provide 100% protection. The vaccine vectors were fast-acting as demonstrated by uniform protection when administered 3 days prior to lethal challenge. Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine.