Optimization of a methamphetamine conjugate vaccine for antibody production in mice.
Optimization of a methamphetamine conjugate vaccine for antibody production in mice.
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甲基苯丙胺结合疫苗的优化小鼠抗体产生。
DOI：
10.1016/j.intimp.2016.03.028
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发表时间：
2016-06
影响因子：
5.6
通讯作者：
Owens SM
中科院分区：
文献类型：
--
作者：
Stevens MW;Gunnell MG;Tawney R;Owens SM
目前仍没有批准的药物用于治疗滥用甲基苯丙胺的患者。治疗尼古丁和可卡因滥用的活疫苗正在临床研究中，但似乎由于抗药物抗体产生不足，尚未证明有效。目前的研究旨在优化甲基苯丙胺结合疫苗ICKLH-SMO9在小鼠体内的组成、佐剂和给药途径，目的是产生显着更高的抗体水平。比较了一系列半抗原表位密度，以及佐剂醛水凝胶和一种新的toll样受体4 （TLR4）激动剂GLA-SE。虽然甲基苯丙胺半抗原密度对抗体反应没有强烈影响，但佐剂却有影响。稳定水包油乳剂（GLA-SE）中葡萄糖吡喃甲酰脂质A在免疫应答中产生的抗体水平远高于醛水凝胶；用GLA-SE免疫也能产生对甲基苯丙胺有较高亲和力的抗体。GLA-SE已被用于流感疫苗的人体研究，与其他一些临床TLR4激动剂一样，它是安全的，并引起强烈的免疫反应。GLA-SE佐剂疫苗通常通过肌肉注射给药，这在这些小鼠研究中也证明是有效的。GLA-SE佐剂的ickhl - smo9甲基苯丙胺疫苗的临床研究有可能通过产生比未成功使用铝基佐剂的药物滥用疫苗高得多的抗体水平来证明其有效性。
There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants.