title: Co-administration of cholera toxin and apple polyphenol extract as a novel and safe mucosal adjuvant strategy.
abstract: Although native cholera toxin (CT) is an extremely effective adjuvant, its toxicity prevents its use in humans. We report here that apple polyphenol extract (APE), obtained from unripe apples, reduces CT-induced morphological changes and cAMP accumulation. Based upon this finding, we have attempted to design a novel, effective and safe mucosal vaccine by using CT with several dosages of APE as nasal adjuvants. Mice nasally immunized with OVA plus CT and an optimal dosage of APE showed significantly reduced levels of inflammatory responses as well as total and OVA-specific IgE antibodies when compared with mice given without APE. However, levels of both mucosal and systemic OVA-specific antibody responses were maintained. Further, APE significantly down-regulated accumulation of CT in the olfactory nerves and epithelium. In summary, an optimal dosage of APE would take full advantage of mucosal adjuvanticity of native CT without any toxicity for application in humans.
authors.affiliation: Department of Microbiology, School of Medicine, Iwate Medical University, Morioka, Iwate, Japan. nyoshino@iwate-med.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Yoshino
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanno
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Ryoki
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Inaba
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Noda
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Sato
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D002726:Chlorogenic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D018928:Immunity, Mucosal; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013634:Tannins / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D005419:Flavonoids; D013634:Tannins; C526219:apple polyphenol extract; D002726:Chlorogenic Acid; D007073:Immunoglobulin E; D010047:Ovalbumin; D002772:Cholera Toxin