Ryuta Uraki1, Zhenyu Piao2, Yukihiro Akeda2, Kiyoko Iwatsuki-Horimoto1, Maki Kiso1, Makoto Ozawa3, Kazunori Oishi4, Yoshihiro Kawaoka5. 1. Division of Virology, Department of Microbiology and Immunology. 2. Laboratory of Clinical Research on Infectious Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University. 3. Laboratory of Animal Hygiene Transboundary Animal Diseases Center, Joint Faculty of Veterinary Medicine, Kagoshima University. 4. 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. 5. 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.
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.
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: F T Cutts; S M A Zaman; G Enwere; S Jaffar; O S Levine; J B Okoko; C Oluwalana; A Vaughan; S K Obaro; A Leach; K P McAdam; E Biney; M Saaka; U Onwuchekwa; F Yallop; N F Pierce; B M Greenwood; R A Adegbola Journal: Lancet Date: 2005 Mar 26-Apr 1 Impact factor: 79.321
Authors: G Neumann; T Watanabe; H Ito; S Watanabe; H Goto; P Gao; M Hughes; D R Perez; R Donis; E Hoffmann; G Hobom; Y Kawaoka Journal: Proc Natl Acad Sci U S A Date: 1999-08-03 Impact factor: 11.205
Authors: Lauri A Hicks; Lee H Harrison; Brendan Flannery; James L Hadler; William Schaffner; Allen S Craig; Delois Jackson; Ann Thomas; Bernard Beall; Ruth Lynfield; Arthur Reingold; Monica M Farley; Cynthia G Whitney Journal: J Infect Dis Date: 2007-10-04 Impact factor: 5.226
Authors: D E Briles; R C Tart; E Swiatlo; J P Dillard; P Smith; K A Benton; B A Ralph; A Brooks-Walter; M J Crain; S K Hollingshead; L S McDaniel Journal: Clin Microbiol Rev Date: 1998-10 Impact factor: 26.132