title: A plant-based system for rapid production of influenza vaccine antigens.
abstract: BACKGROUND
  Influenza virus is a globally important respiratory pathogen that causes a high degree of annual morbidity and mortality. Significant antigenic drift results in emergence of new, potentially pandemic, virus variants. The best prophylactic option for controlling emerging virus strains is to manufacture and administer pandemic vaccines in sufficient quantities and to do so in a timely manner without impacting the regular seasonal influenza vaccine capacity. Current, egg-based, influenza vaccine production is well established and provides an effective product, but has limited capacity and speed.
  
  
  OBJECTIVE
  To satisfy the additional global demand for emerging influenza vaccines, high-performance cost-effective technologies need to be developed. Plants have a potential as an economic and efficient large-scale production platform for vaccine antigens.
  
  
  METHODS
  In this study, a plant virus-based transient expression system was used to produce hemagglutinin (HA) proteins from the three vaccine strains used during the 2008-2009 influenza season, A/Brisbane/59/07 (H1N1), A/Brisbane/10/07 (H3N2), and B/Florida/4/06, as well as from the recently emerged novel H1N1 influenza A virus, A/California/04/09.
  
  
  RESULTS
  The recombinant plant-based HA proteins were engineered and produced in Nicotiana benthamiana plants within 2 months of obtaining the genetic sequences specific to each virus strain. These antigens expressed at the rate of 400-1300 mg/kg of fresh leaf tissue, with >70% solubility. Immunization of mice with these HA antigens induced serum anti-HA IgG and hemagglutination inhibition antibody responses at the levels considered protective against these virus infections.
  
  
  CONCLUSIONS
  These results demonstrate the feasibility of our transient plant expression system for the rapid production of influenza vaccine antigens.
authors.affiliation: Fraunhofer USA Center for Molecular Biotechnology, Newark, DE 19711, USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shoji
authors.forename: Christine E
authors.initials: CE
authors.lastname: Farrance
authors.forename: James
authors.initials: J
authors.lastname: Bautista
authors.forename: Hong
authors.initials: H
authors.lastname: Bi
authors.forename: Konstantin
authors.initials: K
authors.lastname: Musiychuk
authors.forename: April
authors.initials: A
authors.lastname: Horsey
authors.forename: Heewoo
authors.initials: H
authors.lastname: Park
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jaje
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Green
authors.forename: Moneim
authors.initials: M
authors.lastname: Shamloul
authors.forename: Satish
authors.initials: S
authors.lastname: Sharma
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Chichester
authors.forename: Vadim
authors.initials: V
authors.lastname: Mett
authors.forename: Vidadi
authors.initials: V
authors.lastname: Yusibov
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000235:genetics / Q000276:immunology; D014026:Nicotiana / Q000235:genetics* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines