Evaluation of seasonal influenza vaccines for H1N1pdm09 and type B viruses based on a replication-incompetent PB2-KO virus

Hiroki Ui; Seiya Yamayoshi; Ryuta Uraki; Maki Kiso; Kohei Oishi; Shin Murakami; Shigetaka Mimori; Yoshihiro Kawaoka

doi:10.1016/j.vaccine.2017.02.041

Evaluation of seasonal influenza vaccines for H1N1pdm09 and type B viruses based on a replication-incompetent PB2-KO virus

Vaccine. 2017 Apr 4;35(15):1892-1897. doi: 10.1016/j.vaccine.2017.02.041. Epub 2017 Mar 9.

Authors

Hiroki Ui¹, Seiya Yamayoshi², Ryuta Uraki², Maki Kiso², Kohei Oishi², Shin Murakami³, Shigetaka Mimori⁴, Yoshihiro Kawaoka⁵

Affiliations

¹ Vaccine Research Department, Denka Seiken Co., Ltd., Niigata, Japan; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
² Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
³ Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁴ Vaccine Research Department, Denka Seiken Co., Ltd., Niigata, Japan.
⁵ Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: yoshihiro.kawaoka@wisc.edu.

PMID: 28285982
DOI: 10.1016/j.vaccine.2017.02.041

Abstract

Vaccination is the first line of protection against influenza virus infection in humans. Although inactivated and live-attenuated vaccines are available, each vaccine has drawbacks in terms of immunogenicity and safety. To overcome these issues, our group has developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2-expressing cells. Here we generated PB2-KO viruses possessing the hemagglutinin (HA) and neuraminidase (NA) segments from H1N1pdm09 or type B viruses and tested their vaccine potential. The two PB2-KO viruses propagated efficiently in PB2-expressing cells, and expressed chimeric HA as expected. Virus-specific IgG and IgA antibodies were detected in mice immunized with the viruses, and the immunized mice showed milder clinical signs and/or lower virus replication levels in the respiratory tract upon virus challenge. Our results indicate that these PB2-KO viruses have potential as vaccine candidates.

Keywords: PB2-KO virus; Replication-incompetent influenza virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral / blood
Disease Models, Animal
Female
Gene Knockout Techniques*
Immunoglobulin A / blood
Immunoglobulin G / blood
Influenza A Virus, H1N1 Subtype / genetics
Influenza A Virus, H1N1 Subtype / immunology*
Influenza B virus / genetics
Influenza B virus / immunology*
Influenza Vaccines / administration & dosage
Influenza Vaccines / genetics
Influenza Vaccines / immunology*
Mice, Inbred BALB C
Orthomyxoviridae Infections / pathology
Orthomyxoviridae Infections / prevention & control
Respiratory System / virology
Viral Load
Viral Proteins / genetics*

Substances

Antibodies, Viral
Immunoglobulin A
Immunoglobulin G
Influenza Vaccines
PB2 protein, influenza virus
Viral Proteins