Frontline:: A therapeutic vaccine for nicotine dependence:: preclinical efficacy, and phase I safety and immunogenicity
Frontline:: A therapeutic vaccine for nicotine dependence:: preclinical efficacy, and phase I safety and immunogenicity
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DOI：
10.1002/eji.200526285
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发表时间：
2005-07-01
影响因子：
5.4
通讯作者：
Bachmann, MF
中科院分区：
文献类型：
--
作者：
Maurer, P;Jennings, GT;Bachmann, MF
尼古丁是烟草中的主要成瘾成分，并且在摄取后作用于中枢神经系统。大多数吸烟者的戒烟努力都失败了，因为一次滑倒往往会向大脑提供足够的尼古丁，以恢复寻求毒品的行为。通过诱导特异性抗体来阻止尼古丁进入大脑可能是防止这种复发的有效手段。将半抗原尼古丁偶联至由噬菌体Qb的外壳蛋白形成的病毒样颗粒（VLP）。在临床前实验中，该尼古丁-Qb VLP（NicQb）疫苗诱导强烈的抗体应答。静脉内尼古丁激发后，与对照小鼠相比，接种疫苗的小鼠大脑中的尼古丁水平大幅降低。在I期研究中，32名健康的非吸烟者用NicQb免疫。该疫苗是安全的，耐受性良好。所有接受NicQb的志愿者在第7天显示尼古丁特异性IgM抗体，在第14天显示尼古丁特异性IgG抗体。抗体水平可以通过第二次注射或添加明矾作为佐剂来提高，并且抗体对尼古丁具有高亲和力。这些数据表明，由NicQb诱导的抗体可以通过隔离免疫吸烟者血液中的尼古丁来预防复发。
Nicotine is the principal addictive component in tobacco, and following uptake acts in the central nervous system. The smoking-cessation efforts of most smokers fail because a single slip often delivers sufficient nicotine to the brain to reinstate the drug-seeking behaviour. Blocking nicotine from entering the brain by induction of specific antibodies maybe an effective means to prevent such relapses. The hapten nicotine was coupled to virus-like particles (VLP) formed by the coat protein of the bacteriophage Qb. In preclinical experiments, this Nicotine-Qb VLP (NicQb) vaccine induced strong antibody responses. After intravenous nicotine challenge, vaccinated mice exhibited strongly reduced nicotine levels in the brain compared with control mice. In a phase I study, 32 healthy non-smokers were immunized with NicQb. The vaccine was safe and well-tolerated. All volunteers who received NicQb showed nicotine-specific IgM antibodies at day 7 and nicotine-specific IgG antibodies at day 14. Antibody levels could be boosted by a second injection or the addition of Alum as an adjuvant and the antibodies had a high affinity for nicotine. These data suggest that antibodies induced by NicQb may prevent relapses by sequestering nicotine in the blood of immunized smokers.