1. A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia.
- Author
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Ryuta Uraki, Zhenyu Piao, Yukihiro Akeda, Kiyoko Iwatsuki-Horimoto, Maki Kiso, Makoto Ozawa, Kazunori Oishi, Yoshihiro Kawaoka, Uraki, Ryuta, Piao, Zhenyu, Akeda, Yukihiro, Iwatsuki-Horimoto, Kiyoko, Kiso, Maki, Ozawa, Makoto, Oishi, Kazunori, and Kawaoka, Yoshihiro
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GENE knockout , *INFLUENZA viruses , *PNEUMOCOCCAL pneumonia , *LABORATORY mice , *INFLUENZA vaccines , *INTRANASAL medication , *STREPTOCOCCUS pneumoniae , *RECOMBINANT viruses , *PNEUMONIA prevention , *MIXED infections , *ANIMAL experimentation , *BACTERIAL proteins , *BIOLOGICAL models , *GENETIC techniques , *MICE , *ORTHOMYXOVIRUSES , *PNEUMOCOCCAL vaccines , *PROTEINS , *DISEASE complications , *ORTHOMYXOVIRUS infections , *PREVENTION - Abstract
Background: Secondary bacterial infections after influenza can be a serious problem, especially in young children and the elderly, yet the efficacy of current vaccines is limited. Earlier work demonstrated that a replication-incompetent PB2-knockout (PB2-KO) influenza virus possessing a foreign gene in the coding region of its PB2 segment can serve as a platform for a bivalent vaccine.Methods: In the current study, we generated the PB2-KO virus expressing pneumococcal surface protein A (PspA), PB2-KO-PspA virus, the replication of which is restricted to PB2-expressing cells. We then examined the protective efficacy of intranasal immunization with this virus as a bivalent vaccine in a mouse model.Results: High levels of influenza virus-specific and PspA-specific antibodies were induced in the serum and airways of immunized mice. The intranasally immunized mice were protected from lethal doses of influenza virus or Streptococcus pneumoniae. These mice were also completely protected from secondary pneumococcal pneumonia after influenza virus infection.Conclusions: These findings indicate that our recombinant influenza virus serves as a novel and powerful bivalent vaccine against primary and secondary pneumococcal pneumonia as well as influenza. [ABSTRACT FROM AUTHOR]- Published
- 2015
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