title: Oral delivery of wafers made from HBsAg-expressing maize germ induces long-term immunological systemic and mucosal responses.
abstract: BACKGROUND
  The hepatitis B surface antigen (HBsAg) has been administered over the last 20 years as a parenteral vaccine against the hepatitis B virus (HBV). Despite high seroconversion rates, chronic infection rates are still high worldwide. Orally delivered vaccines provide a practical alternative to injected vaccines, potentially helping poorly responding populations and providing a viable alternative for populations in remote locations. Anamnestic responses are vital to establishing the efficacy of a given vaccine and have been assessed in this study using a plant-based oral delivery platform expressing HBsAg.
  
  
  METHODS
  Long-term immunological memory was assessed in mice injected with a primary dose of Recombivax and boosted with orally-delivered HBsAg wafers, control wafers, or parenterally-delivered commercial vaccine (Recombivax).
  
  
  RESULTS
  Mice boosted with HBsAg orally-administered wafers displayed sharp increases in mucosal IgA titers in fecal material and steep increases in serum IgA, whereas mice boosted with Recombivax showed no detectable levels of IgA in either fecal or serum samples following four boosting treatments. Long-term memory in the orally-treated mice was evidenced by sustained fecal IgA, and serum IgA, IgG, and mIU/mL over one year, while Recombivax-treated mice displayed sustained serum IgG and mIU/mL. Furthermore, sharp increases in these same antibodies were induced after re-boosting at 47 and 50 weeks post-primary injection.
  
  
  CONCLUSIONS
  Orally-delivered vaccines can provide long-term immune responses mucosally and systemically. For sexually-transmitted diseases that can be acquired at mucosal surfaces, such as HBV, an oral delivery platform may provide added protection over a conventional parenterally administered vaccine.
authors.affiliation: Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA.
authors.forename: Celine A
authors.initials: CA
authors.lastname: Hayden
authors.affiliation: Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Fischer
authors.affiliation: Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Andrews
authors.affiliation: Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA.
authors.forename: Hayley C
authors.initials: HC
authors.lastname: Chilton
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Debra D
authors.initials: DD
authors.lastname: Turner
authors.affiliation: Department of Statistics, California Polytechnic State University, San Luis Obispo, CA 93407, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Walker
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Tizard
authors.affiliation: Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA. Electronic address: jhoward@appliedbiotech.org.
authors.forename: John A
authors.initials: JA
authors.lastname: Howard
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006510:Hepatitis B Antibodies / Q000032:analysis / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000517:prevention & control*; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000097:blood; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D008807:Mice, Inbred BALB C; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D003313:Zea mays / Q000235:genetics
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; C075655:Recombivax HB; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: Anamnestic response; Bioencapsulation; Immunogenicity; Long-term immune memory; Maize oral vaccine; Mucosal; Plant vaccine; Subunit vaccine; Supercritical fluid extraction