title: Modified pulmonary surfactant is a potent adjuvant that stimulates the mucosal IgA production in response to the influenza virus antigen.
abstract: The intranasal administration of influenza hemagglutinin (HA) vaccine with Surfacten, a modified pulmonary surfactant free of antigenic c-type lectins, as a mucosal adjuvant induced the highest protective mucosal immunity in the airway. The intranasal immunization of mice with HA vaccine (0.2 microg)-Surfacten (0.2 microg) selectively induced the neutralizing anti-HA IgA, but not IgG, and conferred nearly maximal protection in the airway, without inducing a systemic response. In contrast, intranasal inoculation of vaccine with 0.2 microg of the potent mucosal adjuvant cholera toxin B* (CT-B*), prepared by adding 0.2% native CT to the B subunit of CT, induced both anti-HA IgA and IgG in the airway and in the serum. The intranasal administration of HA vaccine alone induced a limited amount of mucosal IgA against influenza virus. Although the s.c. administration of HA vaccine prominently induced serum IgG and IgA, Surfacten and CT-B* did not enhance their induction, and the concentrations of Abs leaking into the airways were insufficient to prevent viral multiplication. The intranasal administration of HA-Surfacten stimulated the expression of MHC class II, CD40, and CD86 molecules in the CD11c-positive cells isolated from the nasal mucosa, but not the expression of cells from the lungs or spleens. Lymphocytes isolated from the airway mucosa after intranasal HA-Surfacten immunization prominently induced TGF-beta1 which, compared with inoculation without Surfacten, promoted an Ag-specific mucosal IgA response. Surfacten alone, however, did not induce TGF-beta1. Our observations suggest that Surfacten, by mimicking the natural surfactant, is an effective mucosal adjuvant in the process of airway immunization.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Mizuno
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ide-Kurihara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichinomiya
authors.forename: Itsuka
authors.initials: I
authors.lastname: Kubo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects*; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007155:Immunologic Factors / Q000494:pharmacology*; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology; D009500:Neutralization Tests; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007252:Influenza Vaccines; D011663:Pulmonary Surfactants; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1