title: A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia.
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.
authors.affiliation: Division of Virology, Department of Microbiology and Immunology.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Uraki
authors.affiliation: Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Piao
authors.affiliation: Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Akeda
authors.affiliation: Division of Virology, Department of Microbiology and Immunology.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Iwatsuki-Horimoto
authors.affiliation: Division of Virology, Department of Microbiology and Immunology.
authors.forename: Maki
authors.initials: M
authors.lastname: Kiso
authors.affiliation: Laboratory of Animal Hygiene Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Division of Virology, Department of Microbiology and Immunology Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo ERATO Infection-Induced Host Responses Project (JST), Saitama, Japan Department of Pathobiological Sciences, University of Wisconsin-Madison.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D060085:Coinfection / Q000517:prevention & control*; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D007252:Influenza Vaccines; C502893:PB2 protein, influenza virus; D022242:Pneumococcal Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C051592:pneumococcal surface protein A
keywords: bivalent vaccine; replication-incompetent influenza virus; secondary pneumococcal pneumonia