一种表达呼吸道合胞病毒 F 蛋白的重组流感病毒疫苗。
A recombinant influenza virus vaccine expressing the F protein of respiratory syncytial virus.
机构信息
Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Mexico, Mexico.
出版信息
Arch Virol. 2014 May;159(5):1067-77. doi: 10.1007/s00705-013-1932-z. Epub 2013 Dec 1.
Abstract
Infections with influenza and respiratory syncytial virus (RSV) rank high among the most common human respiratory diseases worldwide. Previously, we developed a replication-incompetent influenza virus by replacing the coding sequence of the PB2 gene, which encodes one of the viral RNA polymerase subunits, with that of a reporter gene. Here, we generated a PB2-knockout recombinant influenza virus expressing the F protein of RSV (PB2-RSVF virus) and tested its potential as a bivalent vaccine. In mice intranasally immunized with the PB2-RSVF virus, we detected high levels of antibodies against influenza virus, but not RSV. PB2-RSVF virus-immunized mice were protected from a lethal challenge with influenza virus but experienced severe body weight loss when challenged with RSV, indicating that PB2-RSVF vaccination enhanced RSV-associated disease. These results highlight one of the difficulties of developing an effective bivalent vaccine against influenza virus and RSV infections.
摘要
在全球范围内，流感和呼吸道合胞病毒（RSV）感染是最常见的人类呼吸道疾病之一。此前，我们通过替换编码病毒 RNA 聚合酶亚基之一的 PB2 基因的编码序列，开发了一种复制缺陷型流感病毒。在这里，我们生成了一种表达 RSV F 蛋白的 PB2 缺失重组流感病毒（PB2-RSVF 病毒），并测试了其作为二价疫苗的潜力。在通过鼻腔内免疫接种 PB2-RSVF 病毒的小鼠中，我们检测到针对流感病毒的高水平抗体，但没有针对 RSV 的抗体。PB2-RSVF 病毒免疫接种的小鼠对流感病毒的致死性攻击具有保护作用，但在受到 RSV 攻击时体重严重减轻，表明 PB2-RSVF 疫苗接种增强了 RSV 相关疾病。这些结果突出了开发针对流感病毒和 RSV 感染的有效二价疫苗的困难之一。
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