title: In vivo molecular imaging analysis of a nasal vaccine that induces protective immunity against botulism in nonhuman primates.
abstract: Nasal administration is an effective route for a needle-free vaccine. However, nasally administered Ags have the potential to reach the CNS directly from the nasal cavity, thus raising safety concerns. In this study, we performed real-time quantitative tracking of a nasal vaccine candidate for botulism, which is a nontoxic subunit fragment of Clostridium botulinum type A neurotoxin (BoHc/A) effective in the induction of the toxin-neutralizing immune response, by using (18)F-labeled BoHc/A-positron-emission tomography, an in vivo molecular imaging method. This method provides results that are consistent with direct counting of [(18)F] radioactivity or the traditional [(111)In]-radiolabel method in dissected tissues of mice and nonhuman primates. We found no deposition of BoHc/A in the cerebrum or olfactory bulb after nasal administration of (18)F-labeled BoHc/A in both animals. We also established a real-time quantitative profile of elimination of this nasal vaccine candidate and demonstrated that it induces highly protective immunity against botulism in nonhuman primates. Our findings demonstrate the efficiency and safety of a nasal vaccine candidate against botulism in mice and nonhuman primates using in vivo molecular imaging.
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. yukiy@ims.u-tokyo.ac.jp
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Katakai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shibata
authors.forename: Mio
authors.initials: M
authors.lastname: Mejima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tokuhara
authors.forename: Shiho
authors.initials: S
authors.lastname: Kurokawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Fumiko
authors.initials: F
authors.lastname: Ono
authors.forename: Shunji
authors.initials: S
authors.lastname: Kozaki
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics*; D019274:Botulinum Toxins, Type A / Q000276:immunology; D001906:Botulism / Q000000981:diagnostic imaging* / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
chemical_list: D001428:Bacterial Vaccines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D019274:Botulinum Toxins, Type A