Cutting edge: The mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues

We tested the notion that the mucosal adjuvant cholera toxin (CT) could target, in addition to nasal-associated lymhphoreticular tissues, the olfactory nerves/epithelium (ON/E) and ol-factory bulbs (OBs) when given intranasally Radiolaheled CT (I-125-CT) dr CT-B subunit (I-125-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 I-125-tetanus toroid together with unlabeled CT as adjuvant resulted in uptake into the ON/E but not the OB, whereas I-125-tetanus toroid 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.