title: Immunogenicity and protective efficacy of replication-incompetent influenza virus-like particles.
abstract: Despite the success of influenza virus vaccines in reducing severe illness, their efficacy is suboptimal. We describe here the immunogenicity and protective capacity of replication-incompetent influenza virus-like particles (VLPs) which were generated entirely from cDNAs and lacked either the entire NS gene (encoding both the NS1 and NS2 protein) or only the NS2 gene. In mammalian cells infected with NS gene-deficient VLPs, the nucleoprotein, but not other viral proteins including hemagglutinin (HA) and neuraminidase (NA), was detected. In contrast, cells infected with VLPs expressing NS1 but not NS2 (NS2 knockout) expressed multiple viral proteins, including HA and NA. When challenged with lethal doses of an antigenically homologous mouse-adapted influenza virus, 94% of mice vaccinated with the NS2-knockout VLPs survived, compared with less than 10% of those given the NS-deficient VLPs. These results demonstrate the potential of replication-incompetent NS2-knockout VLPs as novel influenza vaccines and perhaps also as vectors to express genes from entirely unrelated pathogens.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Tokiko
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Watanabe
authors.forename: Gabriele
authors.initials: G
authors.lastname: Neumann
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kida
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D001835:Body Weight; D002460:Cell Line; D002642:Chick Embryo; D004274:DNA, Recombinant / Q000235:genetics; D004285:Dogs; D005260:Female; D017353:Gene Deletion; D005814:Genes, Viral / Q000235:genetics; D006801:Humans; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D015996:Survival Rate; D013997:Time Factors; D014611:Vaccination; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D004274:DNA, Recombinant; D007252:Influenza Vaccines; C108309:NS protein, influenza virus; D017361:Viral Nonstructural Proteins