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Vaccination against Influenza with Recombinant Hemagglutinin Expressed by Schizochytrium sp. Confers Protective Immunity
Authors:Anne-Cécile V. Bayne  David Boltz  Carole Owen  Yelena Betz  Goncalo Maia  Parastoo Azadi  Stephanie Archer-Hartmann  Ross Zirkle  J. Casey Lippmeier
Affiliation:1. Nutritional Lipids, DSM Nutritional Products, Columbia, Maryland, United States of America.; 2. Division of Microbiology & Molecular Biology, IIT Research Institute, Illinois Institute of Technology, Chicago, Illinois, United States of America.; 3. Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, United States of America.; St. Jude Children''s Research Hospital, United States of America,
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.
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