J Infect Dis. A bivalent vaccine based on a PB2-knockout influenza virus protects mice from secondary pneumococcal pneumonia

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1. J Infect Dis. (2015) doi: 10.1093/infdis/jiv341 First published online: June 29, 2015
   [h=1]A bivalent vaccine based on a PB2-knockout influenza virus protects mice from secondary pneumococcal pneumonia[/h]
   • Ryuta Uraki1,?,
   • Zhenyu Piao2,?,
   • Yukihiro Akeda2,
   • Kiyoko Iwatsuki-Horimoto1,
   • Maki Kiso1,
   • Makoto Ozawa3,4,
   • Kazunori Oishi2,5 and
   • Yoshihiro Kawaoka1,6,7,8,*
   • [SUP]1[/SUP]Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo
   • [SUP]2[/SUP]Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka
   • [SUP]3[/SUP]Laboratory of Animal Hygiene, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima
   • [SUP]4[/SUP]Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima
   • [SUP]5[/SUP]Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo
   • [SUP]6[/SUP]ERATO Infection-Induced Host Responses Project (JST), Saitama, Japan
   • [SUP]7[/SUP]Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison , USA
   • [SUP]8[/SUP]Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan
   • ↵*Corresponding author: Corresponding author's mailing address: Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, Japan. Phone: +81-3-5449-5504. Fax: +81-3-5449-5408. E-mail: kawaoka{at}ims.u-tokyo.ac.jp.
   • ↵? These authors contributed equally to this work.
   
   [h=2]Abstract[/h] Background.  Secondary bacterial infections following influenza can be a serious problem, especially in young children and the elderly. Yet, the efficacy of current vaccines is limited. We previously 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. Here, we generated the PB2-KO virus expressing pneumococcal surface protein A (PspA), PB2KO-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 following 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.
   
   
   
   http://jid.oxfordjournals.org/content/early/2015/06/28/infdis.jiv341.abstract