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The Journal of Immunology, 2000, 165: 4778-4782.
Copyright © 2000 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: The Mucosal Adjuvant Cholera Toxin Redirects Vaccine Proteins into Olfactory Tissues

Frederik W. van Ginkel*, Raymond J. Jackson*, Yoshikazu Yuki{dagger} and Jerry R. McGhee2,*

* Department of Microbiology, Immunobiology Vaccine Center, University of Alabama, Birmingham, AL 35294; and {dagger} JCR Biopharmaceuticals, San Diego, CA 92121

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 (125I-CT) or CT-B subunit (125I-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 125I-tetanus toxoid together with unlabeled CT as adjuvant resulted in uptake into the ON/E but not the OB, whereas 125I-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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