title: Surfactant protein C is an essential constituent for mucosal adjuvanticity of Surfacten, acting as an antigen delivery vehicle and inducing both local and systemic immunity.
abstract: We have reported that Surfacten(®) (St), a bovine pulmonary surfactant free of antigenic c-type lectins, is a useful mucosal adjuvant for nasal vaccination. To prepare ample supplies a synthetic adjuvant that mimics St, we analyzed essential constituents of St for mucosal adjuvanticity. Intranasal inoculation of influenza virus hemagglutinin (HA) vaccine combined with St free of surfactant protein (SP)-C resulted in failure of HA vaccine delivery to dendritic cells and loss of local and systemic immune responses. Naïve bovine SP-C, synthetic human or bovine SP-C peptide reconstituted with three major St lipids restored delivery activity and local and systemic immune responses to levels similar to those of St and provided almost complete protection against lethal doses of influenza virus challenge in mice. The delivery of fluoresceinated HA vaccine to cultured dendritic cells was significantly enhanced by co-administration of St or synthetic adjuvant, and moderately stimulated the expression of MHC class II and CD86. In addition, both St and synthetic adjuvant markedly sustained HA vaccine and achieved a wide antigen distribution in murine nasal cavity. These results suggest that synthetic mucosal adjuvant reconstituted with SP-C peptide and major St lipids is useful for ample supply of the potent mucosal adjuvant as an antigen delivery vehicle for intranasal vaccination.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, Tokushima 770-8503, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Mizuno
authors.forename: Takashi
authors.initials: T
authors.lastname: Kimoto
authors.forename: Tsunetomo
authors.initials: T
authors.lastname: Takei
authors.forename: Akiho
authors.initials: A
authors.lastname: Fukuta
authors.forename: Wakako
authors.initials: W
authors.lastname: Shinahara
authors.forename: Etsuhisa
authors.initials: E
authors.lastname: Takahashi
authors.forename: Mihiro
authors.initials: M
authors.lastname: Yano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis; D001688:Biological Products / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D018928:Immunity, Mucosal / Q000187:drug effects*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D055666:Lipopeptides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D010456:Peptides, Cyclic / Q000494:pharmacology*; D012376:Rodent Diseases / Q000517:prevention & control / Q000821:virology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; D001688:Biological Products; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; D055666:Lipopeptides; D010456:Peptides, Cyclic; D022223:Vaccines, Subunit; C009365:surfactin peptide