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A Replication-Incompetent PB2-Knockout Influenza A Virus Vaccine Vector

  作者 Victor, ST; Watanabe, S; Katsura, H; Ozawa, M; Kawaoka, Y  
  选自 期刊  Journal of virology;  卷期  2012年86-8;  页码  4123-4128  
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[摘要]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.

 
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