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.