1. A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia
- Author
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Yukihiro Akeda, Maki Kiso, Ryuta Uraki, Kiyoko Iwatsuki-Horimoto, Kazunori Oishi, Yoshihiro Kawaoka, Zhenyu Piao, and Makoto Ozawa
- Subjects
viruses ,medicine.disease_cause ,Bivalent (genetics) ,Virus ,law.invention ,Pneumococcal Vaccines ,Gene Knockout Techniques ,Mice ,Viral Proteins ,Major Articles and Brief Reports ,Bacterial Proteins ,Orthomyxoviridae Infections ,law ,Streptococcus pneumoniae ,Animals ,Immunology and Allergy ,Medicine ,Gene ,Administration, Intranasal ,Vaccines, Synthetic ,biology ,Coinfection ,business.industry ,food and beverages ,virus diseases ,Pneumonia, Pneumococcal ,biochemical phenomena, metabolism, and nutrition ,Orthomyxoviridae ,medicine.disease ,Virology ,respiratory tract diseases ,Disease Models, Animal ,Infectious Diseases ,Influenza Vaccines ,Immunology ,Pneumococcal pneumonia ,Recombinant DNA ,biology.protein ,Nasal administration ,Antibody ,business - 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.
- Published
- 2015