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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
A Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice From Secondary Pneumococcal Pneumonia
Ryuta Uraki1, Zhenyu Piao2, Yukihiro Akeda2
1Division of Virology, Department of Microbiology and Immunology.
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.
Insights
A novel bivalent vaccine using a knockout influenza virus expressing pneumococcal surface protein A (PspA) effectively protects against influenza and secondary pneumococcal pneumonia in mice.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Secondary bacterial infections post-influenza pose significant risks, particularly to vulnerable populations.
- Current influenza vaccines have limited efficacy against these secondary infections.
- A replication-incompetent PB2-knockout (PB2-KO) influenza virus platform was previously shown to support bivalent vaccine development.
Purpose of the Study:
- To develop and evaluate a novel bivalent vaccine candidate.
- To assess the protective efficacy of a PB2-KO influenza virus expressing pneumococcal surface protein A (PspA) against influenza and pneumococcal pneumonia.
Main Methods:
- Generated a PB2-knockout influenza virus engineered to express PspA (PB2-KO-PspA).
- Administered the PB2-KO-PspA virus intranasally to a mouse model.
- Assessed the induction of virus-specific and PspA-specific antibodies.
- Challenged immunized mice with lethal doses of influenza virus and Streptococcus pneumoniae.
Main Results:
- Intranasal immunization with PB2-KO-PspA induced high levels of influenza and PspA-specific antibodies in serum and airways.
- Immunized mice showed protection against lethal influenza virus and Streptococcus pneumoniae challenges.
- Complete protection was observed against secondary pneumococcal pneumonia following influenza infection.
Conclusions:
- The recombinant influenza virus (PB2-KO-PspA) functions as a potent bivalent vaccine.
- This novel vaccine platform offers protection against primary influenza and secondary pneumococcal pneumonia.
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