title: Vaccination against influenza with recombinant hemagglutinin expressed by Schizochytrium sp. confers protective immunity.
abstract: For the rapid production of influenza vaccine antigens in unlimited quantities, a transition from conventional egg-based production to cell-based and recombinant systems is required. The need for higher-yield, lower-cost, and faster production processes is critical to provide adequate supplies of influenza vaccine to counter global pandemic threats. In this study, recombinant hemagglutinin proteins of influenza virus were expressed in the microalga Schizochytrium sp., an established, fermentable organism grown in large scale for the manufacture of polyunsaturated fatty acids for animal and human health applications. Schizochytrium was capable of exporting the full-length membrane-bound proteins in a secreted form suitable for vaccine formulation. One recombinant hemagglutinin (rHA) protein derived from A/Puerto Rico/8/34 (H1N1) influenza virus was evaluated as a vaccine in a murine challenge model. Protective immunity from lethal challenge with homologous virus was elicited by a single dose of 1.7, 5 or 15 µg rHA with or without adjuvant at survival rates between 80-100%. Full protection (100%) was established at all dose levels with or without adjuvant when mice were given a second vaccination. These data demonstrate the potential of Schizochytrium sp. as a platform for the production of recombinant antigens useful for vaccination against influenza.
authors.affiliation: Nutritional Lipids, DSM Nutritional Products, Columbia, Maryland, United States of America.
authors.forename: Anne-Cécile V
authors.initials: AC
authors.lastname: Bayne
authors.forename: David
authors.initials: D
authors.lastname: Boltz
authors.forename: Carole
authors.initials: C
authors.lastname: Owen
authors.forename: Yelena
authors.initials: Y
authors.lastname: Betz
authors.forename: Goncalo
authors.initials: G
authors.lastname: Maia
authors.forename: Parastoo
authors.initials: P
authors.lastname: Azadi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Archer-Hartmann
authors.forename: Ross
authors.initials: R
authors.lastname: Zirkle
authors.forename: J Casey
authors.initials: JC
authors.lastname: Lippmeier
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D058086:Microalgae / Q000235:genetics*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D058009:Stramenopiles / Q000235:genetics*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins