title: Immunogenicity of H1N1 influenza virus-like particles produced in Nicotiana benthamiana.
abstract: The H1N1 influenza pandemic of 2009 stimulated interest in developing safe and effective subunit influenza vaccines using rapid and cost-effective recombinant technologies that can avoid dependence on hens' eggs supply and live viruses for production. Among alternative approaches to subunit vaccine development, virus-like particles (VLPs) represent an attractive strategy due to their safety and immunogenicity. Previously, we have produced a recombinant monomeric hemagglutinin (HA) protein derived from the A/California/04/09 (H1N1) strain of influenza virus in a plant-based transient expression system and demonstrated immunogenicity and safety of this monomeric HA in animal models and human volunteers. In an effort to produce higher potency influenza vaccine in plants, we have designed and generated enveloped VLPs using the ectodomain of HA from the A/California/04/09 strain and heterologous sequences. The resulting H1 HA VLPs (HAC-VLPs) elicited robust hemagglutination inhibition antibody responses in mice at doses lower than 1 µg in the presence or absence of Alhydrogel adjuvant. These results suggest enhanced immunogenicity of recombinant HA in the form of an enveloped VLP over soluble antigen.
authors.affiliation: a Fraunhofer USA Center for Molecular Biotechnology; Newark, DE USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shoji
authors.forename: Alex
authors.initials: A
authors.lastname: Prokhnevsky
authors.forename: Brett
authors.initials: B
authors.lastname: Leffet
authors.forename: Nancy
authors.initials: N
authors.lastname: Vetter
authors.forename: Stephen
authors.initials: S
authors.lastname: Tottey
authors.forename: Shama
authors.initials: S
authors.lastname: Satinover
authors.forename: Konstantin
authors.initials: K
authors.lastname: Musiychuk
authors.forename: Moneim
authors.initials: M
authors.lastname: Shamloul
authors.forename: Joey
authors.initials: J
authors.lastname: Norikane
authors.forename: R Mark
authors.initials: RM
authors.lastname: Jones
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Green
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Streatfield
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification*; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D014026:Nicotiana / Q000235:genetics; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle; D000536:Aluminum Hydroxide
keywords: hemagglutinin; influenza; plant-based production; subunit vaccine; transient expression; virus-like particle