title: Insect larvae biofactories as a platform for influenza vaccine production.
abstract: Increased production capacity is one of the most important priorities for seasonal and pandemic influenza vaccines. In the present study, we used a baculovirus-insect larvae system (considered small, living biofactories) to improve the production of recombinant influenza virus H1N1 hemagglutinin (HA). Insect larvae produced four-fold more HA protein than insect cells per biomass unit (1 g of fresh larvae weight). A single infected Trichoplusia ni larva produced up to 113 μg of soluble and easily purified recombinant HA, an amount similar to that produced by 1.2×10(8) Sf21 insect cells infected by the same baculovirus. The use of the KDEL endoplasmic reticulum retention signal fused to the HA protein further increased recombinant protein production. Larvae-derived HA was immunogenically functional in vaccinated mice, inducing the generation of hemagglutination inhibition antibodies and a protective immune response against a lethal challenge with a highly virulent virus. The productivity, scalability and cost efficiency of small, living biofactories based on insect larvae suggest a broad-based strategy for the production of recombinant subunit vaccines against seasonal or pandemic influenza as an alternative to fermentation technologies.
authors.affiliation: Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain. casado@inia.es
authors.forename: E
authors.initials: E
authors.lastname: Gomez-Casado
authors.forename: S
authors.initials: S
authors.lastname: Gomez-Sebastian
authors.forename: M C
authors.initials: MC
authors.lastname: Núñez
authors.forename: R
authors.initials: R
authors.lastname: Lasa-Covarrubias
authors.forename: S
authors.initials: S
authors.lastname: Martínez-Pulgarín
authors.forename: J M
authors.initials: JM
authors.lastname: Escribano
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D006801:Humans; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000276:immunology; D007252:Influenza Vaccines / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D007814:Larva / Q000821:virology; D051379:Mice; D009036:Moths / Q000821:virology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000627:therapeutic use
chemical_list: C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic