title: Intranasal influenza vaccination using a new synthetic mucosal adjuvant SF-10: induction of potent local and systemic immunity with balanced Th1 and Th2 responses.
abstract: BACKGROUND
  We found previously that bovine pulmonary Surfacten® used in newborns with acute respiratory distress syndrome is a safe and efficacious antigen vehicle for intranasal vaccination.
  
  
  OBJECTIVE
  The objective of this study was to industrially produce a synthetic adjuvant mimicking Surfacten® for clinical use without risk of bovine spongiform encephalopathy.
  
  
  METHODS
  We selected three Surfacten lipids and surfactant protein (SP)-C as essential constituents for adjuvanticity. For replacement of the hydrophobic SP-C, we synthesized SP-related peptides and analyzed their adjuvanticity. We evaluated lyophilization to replace sonication for the binding of influenza virus hemagglutinin (HA) to the synthetic adjuvant. We also added a carboxy vinyl polymer (CVP) to the synthetic adjuvant and named the mixture as SF-10 adjuvant. HA combined with SF-10 was administered intranasally to mice, and induction of nasal-wash HA-specific secretory IgA (s-IgA) and serum IgG with Th1-/Th2-type cytokine responses in nasal cavity and virus challenge test were assessed.
  
  
  CONCLUSIONS
  Intranasal immunization with HA-SF-10 induced significantly higher levels of anti-HA-specific nasal-wash s-IgA and serum IgG than those induced by HA-poly(I:C), a reported potent mucosal vaccine, and provided highly efficient protection against lethal doses of virus challenge in mice. Anti-HA-specific serum IgG levels induced by HA-SF-10 were almost equivalent to those induced by subcutaneous immunization of HA twice. Intranasal administration of HA-SF-10 induced balanced anti-HA-specific IgG1 and IgG2a in sera and IFN-γ- and IL-4-producing lymphocytes in nasal cavity without any induction of anti-HA IgE. The results suggest that HA-SF-10 is a promising nasal influenza vaccine and that SF-10 can be supplied in large quantities commercially.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimoto
authors.forename: Dai
authors.initials: D
authors.lastname: Mizuno
authors.forename: Tsunetomo
authors.initials: T
authors.lastname: Takei
authors.forename: Takuya
authors.initials: T
authors.lastname: Kunimi
authors.forename: Shinji
authors.initials: S
authors.lastname: Ono
authors.forename: Satoko
authors.initials: S
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001769:Blood / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines
keywords: Pulmonary surfactant; Th1/Th2 responses; influenza vaccine; nasal vaccination; synthetic mucosal adjuvant