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

      The Journal of Immunology Author Choice

      Adjuvants, Immunologic, administration & dosage, pharmacokinetics, Administration, Intranasal, Animals, Axonal Transport, immunology, Brain, metabolism, Cholera Toxin, Cholera Vaccines, G(M1) Ganglioside, physiology, Iodine Radioisotopes, Mice, Mice, Inbred C57BL, Nasal Mucosa, innervation, Neurons, Olfactory Bulb, Olfactory Nerve, Organ Specificity, Peptide Fragments, Tissue Distribution

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          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.

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