A replication-incompetent PB2-knockout influenza A virus vaccine vector.
Vaccination is the primary form of protection from influenza virus infection. We recently developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that possesses a reporter gene (the green fluorescent protein gene) in the coding region of the PB2 segment. This virus replicated to high titers in PB2-expressing, but not unmodified, cells, suggesting its potential safety and feasibility as a vaccine. Here, we tested its efficacy in a murine model. The levels of IgG and IgA antibodies against influenza virus in sera, nasal washes, and bronchoalveolar lavage fluids of mice immunized with the PB2-KO virus were higher than those induced by a conventional inactivated vaccine. All PB2-KO virus-immunized mice survived challenges with lethal doses of influenza virus. Moreover, importantly, mice immunized with the PB2-KO virus produced antibodies against the reporter protein, suggesting that the PB2-KO virus has potential as a multivalent vaccine to combat infection with not only influenza virus but also other pathogens.
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Sylvia T
ST
Victor
Shinji
S
Watanabe
Hiroaki
H
Katsura
Makoto
M
Ozawa
Yoshihiro
Y
Kawaoka
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001835:Body Weight; D004285:Dogs; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D014420:Turbinates / Q000821:virology; D014779:Virus Replication / Q000235:genetics*
D000914:Antibodies, Viral; D007252:Influenza Vaccines