In Vivo Molecular Imaging Analysis of a Nasal Vaccine That Induces Protective Immunity against Botulism in Nonhuman Primates
In Vivo Molecular Imaging Analysis of a Nasal Vaccine That Induces Protective Immunity against Botulism in Nonhuman Primates
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DOI：
10.4049/jimmunol.1001789
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发表时间：
2010-11-01
影响因子：
4.4
通讯作者：
Kiyono, Hiroshi
中科院分区：
文献类型：
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作者：
Yuki, Yoshikazu;Nochi, Tomonori;Kiyono, Hiroshi
鼻腔给药是无针疫苗的有效途径。然而，鼻内给药的Ag有可能直接从鼻腔到达CNS，因此引起了安全性问题。在这项研究中，我们进行了实时定量跟踪的鼻疫苗候选肉毒中毒，这是一个无毒的亚单位片段肉毒梭菌A型神经毒素（BoHc/A）有效的诱导毒素中和免疫反应，通过使用（18）F-标记的BoHc/A-正电子发射断层扫描，在体内分子成像方法。该方法提供的结果与小鼠和非人灵长类动物解剖组织中[（18）F]放射性直接计数或传统[（111）In]-放射性标记方法一致。我们发现，在这两种动物鼻腔给药（18）F-标记的BoHc/A后，大脑或嗅球中没有BoHc/A的沉积。我们还建立了消除这种鼻疫苗候选物的实时定量曲线，并证明它在非人灵长类动物中诱导针对肉毒杆菌中毒的高度保护性免疫。我们的研究结果证明了使用体内分子成像的小鼠和非人灵长类动物中肉毒杆菌中毒鼻疫苗候选物的有效性和安全性。免疫学杂志，2010，185：5436-5443。
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.