徳島大学 教育・研究者情報データベース(EDB)

1. (英) Hagiwara Yukari

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2. (英) Kawamura I. Yuki

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3. 片岡 宏介([徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.口腔保健学系.口腔保健福祉学]/徳島大学.大学院医歯薬学研究部.歯学域.口腔科学部門.歯学系.予防歯学令和6年4月より併任)

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4. (英) Rahima Bibi

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5. (英) Jackson J. Raymond

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6. (英) Komase Katsuhiro

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7. (英) Dohi Taeko

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8. (英) Boyaka N. Prosper

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9. (英) Takeda Yoshifumi

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10. (英) Kiyono Hiroshi

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11. (英) McGhee R. Jerry

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12. (英) Fujihashi Kohtaro

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(英) A second generation of double mutant cholera toxin adjuvants: enhanced immunity without intracellular trafficking.

(英) Nasal application of native cholera toxin (nCT) as a mucosal adjuvant has potential toxicity for the CNS through binding to GM1 gangliosides in the olfactory nerves. Although mutants of cholera toxin (mCTs) have been developed that show mucosal adjuvant activity without toxicity, it still remains unclear whether these mCTs will induce CNS damage. To help overcome these concerns, in this study we created new double mutant CTs (dmCTs) that have two amino acid substitutions in the ADP-ribosyltransferase active center (E112K) and COOH-terminal KDEL (E112K/KDEV or E112K/KDGL). Confocal microscopic analysis showed that intracellular localization of dmCTs differed from that of mCTs and nCTs in intestinal epithelial T84 cells. Furthermore, both dmCTs exhibited very low toxicity in the Y1 cell assay and mouse ileal loop tests. When mucosal adjuvanticity was examined, both dmCTs induced enhanced OVA-specific immune responses in both mucosal and systemic lymphoid tissues. Interestingly, although both dmCT E112K/KDEV and dmCT E112K/KDGL showed high Th2-type and significant Th1-type cytokine responses by OVA-specific CD4+ T cells, dmCT E112K/KDEV exhibited significantly lower Th1-type cytokine responses than did nCT and dmCT E112K/KDGL. These results show that newly developed dmCTs retain strong biological adjuvant activity without CNS toxicity.

1. (英) Adjuvants, Immunologic
2. (英) Animals
3. (英) Antibodies
4. (英) CD4-Positive T-Lymphocytes
5. (英) Cell Proliferation
6. 中枢神経系(central nervous system)
7. (英) Cholera Toxin
8. 細胞質分裂(cytokinesis)
9. 小胞体(endoplasmic reticulum)
10. (英) Golgi Apparatus
11. (英) Immunity, Mucosal
12. (英) Mice
13. (英) Mice, Inbred C57BL
14. (英) Mutation
15. (英) Olfactory Bulb
16. (英) Ovalbumin
17. (英) Protein Transport

1. (英) Article.Affiliation: Department of Pediatric Dentistry, Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, N.I.H., Extramural

4. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't