Though cocaine abuse and addiction continue to have serious implications for health and society, no FDA-approved interventions have been developed. Anticocaine conjugate vaccines offer an attractive opportunity for addiction treatment; however, vaccines have thus far failed in clinical trials. As a result, anticocaine vaccines must be further optimized to achieve clinical translation. Herein, we report a study on the relationship between vaccine efficacy and hapten stability toward hydrolysis. Two haptens developed by our laboratory, GND and GNE, were conjugated to tetanus toxoid (TT) and formulated with alum and cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826) adjuvants, the optimal formulation in anticocaine vaccine design. GND, a diamide, is more hydrolytically stable than GNE, a monoamide, toward butyrylcholinesterases. Ultimately, both vaccines induced antibodies with high affinity for cocaine. In hyperlocomotion testing, GND-TT and GNE-TT vaccinated mice exhibited a robust blockade of cocaine's stimulatory effects at all tested doses. Overall, antibodies raised against both haptens were highly effective in protecting mice from cocaine-induced psychostimulation.

中文翻译：

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可卡因疫苗的有效合成及其体内评价。

尽管可卡因滥用和成瘾继续对健康和社会产生严重影响，但尚未开发出FDA批准的干预措施。抗可卡因结合疫苗为成瘾治疗提供了诱人的机会。然而，疫苗迄今在临床试验中失败了。结果，必须进一步优化抗可卡因疫苗以实现临床翻译。在本文中，我们报告了疫苗功效与半抗原对水解的稳定性之间的关系的研究。我们实验室开发的两个半抗原GND和GNE与破伤风类毒素（TT）结合，并与明矾和胞嘧啶-鸟嘌呤寡聚脱氧核苷酸1826（CpG ODN 1826）佐剂一起配制，这是抗可卡因疫苗设计中的最佳制剂。GND（一种二酰胺）比GNE（一种单酰胺）对丁酰胆碱酯酶的水解稳定性更高。最终，两种疫苗都诱导了对可卡因具有高度亲和力的抗体。在超运动测试中，接种GND-TT和GNE-TT的小鼠在所有测试剂量下均表现出强大的可卡因刺激作用。总体而言，针对两种半抗原产生的抗体在保护小鼠免受可卡因诱导的精神刺激作用方面非常有效。