title: Nasally administered cholera toxin A-subunit acts as a mucosal adjuvant.
abstract: It is well established that cholera toxin (CT) produced by Vibrio cholerae acts as a potent mucosal adjuvant; however, the native form of this molecule causes severe diarrhea. Furthermore, both native CT and its B-subunit derivative bind to monosialogangliosides (GM1) in membrane raft micro-domains on neural tissues and are thus unsuitable for use in humans. In this study, we evaluated the adjuvanticity of the CT A-subunit (CT-A) administered with ovalbumin (OVA) by the nasal route. We found that nasal administration of OVA plus CT-A elicited both mucosal and systemic antibody (Ab) responses. Immunization of mice with OVA plus CT-A resulted in the induction of OVA-specific IgA Abs in saliva and nasal secretions. Furthermore, significant OVA-specific serum immunoglobulin (Ig) G and IgA Ab responses were induced. Antibody-forming cell (AFC) analysis confirmed the Ab titer findings by revealing significant numbers of OVA-specific IgA AFCs in submandibular glands. In addition, splenic lymphocytes restimulated with OVA in vitro exhibited significant proliferative responses. Thus, CT-A might be a candidate for an effective adjuvant for inducing antigen (Ag)-specific Ab responses in human systemic and mucosal compartments, such as the oral cavity.
authors.affiliation: Department of Pathology, Nihon University School of Dentistry at Matsudo, Chiba 271-8587. ottis@mac.com
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Campos
authors.forename: Jun
authors.initials: J
authors.lastname: Namikoshi
authors.forename: Satomi
authors.initials: S
authors.lastname: Maeba
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000187:drug effects*; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000276:immunology*; D018928:Immunity, Mucosal / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D010047:Ovalbumin; D002772:Cholera Toxin