In vivo molecular imaging analysis of a nasal vaccine that induces protective immunity against botulism in nonhuman primates.
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.
Yuki
Yoshikazu
Y
Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan. yukiy@ims.u-tokyo.ac.jp
Nochi
Tomonori
T
Harada
Norihiro
N
Katakai
Yuko
Y
Shibata
Hiroaki
H
Mejima
Mio
M
Kohda
Tomoko
T
Tokuhara
Daisuke
D
Kurokawa
Shiho
S
Takahashi
Yuko
Y
Ono
Fumiko
F
Kozaki
Shunji
S
Terao
Keiji
K
Tsukada
Hideo
H
Kiyono
Hiroshi
H
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
D001428:Bacterial Vaccines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D019274:Botulinum Toxins, Type A