title: Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues.
abstract: We tested the notion that the mucosal adjuvant cholera toxin (CT) could target, in addition to nasal-associated lymphoreticular tissues, the olfactory nerves/epithelium (ON/E) and olfactory bulbs (OBs) when given intranasally. Radiolabeled CT ((125)I-CT) or CT-B subunit ((125)I-CT-B), when given intranasally to mice, entered the ON/E and OB and persisted for 6 days; however, neither molecule was present in nasal-associated lymphoreticular tissues beyond 24 h. This uptake into olfactory regions was monosialoganglioside (GM1) dependent. Intranasal vaccination with (125)I-tetanus toxoid together with unlabeled CT as adjuvant resulted in uptake into the ON/E but not the OB, whereas (125)I-tetanus toxoid alone did not penetrate into the CNS. We conclude that GM1-binding molecules like CT target the ON/E and are retrograde transported to the OB and may promote uptake of vaccine proteins into olfactory neurons. This raises concerns about the role of GM1-binding molecules that target neuronal tissues in mucosal immunity.
authors.affiliation: Department of Microbiology, Immunobiology Vaccine Center, University of Alabama, Birmingham, AL 35294, USA.
authors.forename: F W
authors.initials: FW
authors.lastname: van Ginkel
authors.forename: R J
authors.initials: RJ
authors.lastname: Jackson
authors.forename: Y
authors.initials: Y
authors.lastname: Yuki
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000281:Administration, Intranasal; D000818:Animals; D001370:Axonal Transport / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D005677:G(M1) Ganglioside / Q000502:physiology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology* / Q000294:innervation*; D009474:Neurons / Q000276:immunology / Q000378:metabolism; D009830:Olfactory Bulb / Q000276:immunology / Q000378:metabolism; D009832:Olfactory Nerve / Q000276:immunology / Q000378:metabolism; D009928:Organ Specificity / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D022121:Cholera Vaccines; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D005677:G(M1) Ganglioside; D002772:Cholera Toxin