A Replication-Incompetent PB2-Knockout Influenza A Virus Vaccine Vector
A Replication-Incompetent PB2-Knockout Influenza A Virus Vaccine Vector
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DOI：
10.1128/jvi.06232-11
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发表时间：
2012-04-01
影响因子：
5.4
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
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作者：
Victor, Sylvia T.;Watanabe, Shinji;Kawaoka, Yoshihiro
疫苗接种是预防流感病毒感染的主要形式。我们最近开发了一种复制能力不强的PB2敲除（PB2- ko）流感病毒，该病毒在PB2片段的编码区拥有一个报告基因（绿色荧光蛋白基因）。这种病毒在表达pb2的细胞中复制到高滴度，但不是未经修饰的细胞，这表明它作为疫苗的潜在安全性和可行性。在这里，我们在小鼠模型中测试了它的功效。接种PB2-KO病毒的小鼠血清、鼻洗液和支气管肺泡灌洗液中抗流感病毒IgG和IgA抗体水平高于常规灭活疫苗诱导的小鼠。所有PB2-KO病毒免疫的小鼠在致命剂量的流感病毒攻击中存活。此外，重要的是，用PB2-KO病毒免疫的小鼠产生了针对报告蛋白的抗体，这表明PB2-KO病毒有潜力作为一种多价疫苗，不仅可以对抗流感病毒感染，还可以对抗其他病原体感染。
Vaccination is the primary form of protection from influenza virus infection. We recently developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that possesses a reporter gene (the green fluorescent protein gene) in the coding region of the PB2 segment. This virus replicated to high titers in PB2-expressing, but not unmodified, cells, suggesting its potential safety and feasibility as a vaccine. Here, we tested its efficacy in a murine model. The levels of IgG and IgA antibodies against influenza virus in sera, nasal washes, and bronchoalveolar lavage fluids of mice immunized with the PB2-KO virus were higher than those induced by a conventional inactivated vaccine. All PB2-KO virus-immunized mice survived challenges with lethal doses of influenza virus. Moreover, importantly, mice immunized with the PB2-KO virus produced antibodies against the reporter protein, suggesting that the PB2-KO virus has potential as a multivalent vaccine to combat infection with not only influenza virus but also other pathogens.