期刊
JOURNAL OF IMMUNOLOGY
卷 185, 期 9, 页码 5436-5443出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1001789
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资金
- Bio-oriented Technology Research Advancement Institution
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Core Research for Engineering, Science, and Technology, Japan Science and Technology Agency
- Ministry of Health and Welfare of Japan
- Center of Education and Research for the Advanced Genome-based Medicine for Personalized Medicine and the Control of Worldwide Infectious Diseases
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. The Journal of Immunology, 2010, 185: 5436-5443.
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