title: Residual baculovirus in insect cell-derived influenza virus-like particle preparations enhances immunogenicity.
abstract: Influenza virus-like particles are currently evaluated in clinical trials as vaccine candidates for influenza viruses. Most commonly they are produced in baculovirus- or mammalian- expression systems. Here we used different vaccination schemes in order to systematically compare virus-like particle preparations generated in the two systems. Our work shows significant differences in immunogenicity between the two, and indicates superior and broader immune responses induced by the baculovirus-derived constructs. We demonstrate that these differences critically influence protection and survival in a mouse model of influenza virus infection. Finally, we show that the enhanced immunogenicity of the baculovirus-derived virus-like particles is caused by contamination with residual baculovirus which activates the innate immune response at the site of inoculation.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Irina
authors.initials: I
authors.lastname: Margine
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Gil
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Chou
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006385:Hemagglutination Inhibition Tests; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D060888:Real-Time Polymerase Chain Reaction; D061987:Sf9 Cells; D018411:Spodoptera; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D017931:DNA Primers; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle; D016899:Interferon-beta