Improvements on a chemically contiguous hapten for a vaccine to address fentanyl-contaminated heroin.
Improvements on a chemically contiguous hapten for a vaccine to address fentanyl-contaminated heroin.
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DOI：
10.1016/j.bmc.2021.116225
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发表时间：
2021-05
影响因子：
3.5
通讯作者：
Hyeri Park;J. Lee;L. M. Eubanks;Beverly Ellis;Bin Zhou;K. Janda
中科院分区：
文献类型：
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作者：
Hyeri Park;J. Lee;L. M. Eubanks;Beverly Ellis;Bin Zhou;K. Janda
由于阿片类药物和精神兴奋剂中掺入芬太尼，导致与阿片类药物和精神兴奋剂相关的意外过量死亡的发生率有所增加。非法化合物和芬太尼之间的协同作用会导致呼吸抑制加剧，导致意外死亡。在不断扩大的阿片类药物流行中实施的传统小分子疗法存在许多问题，因为它们与滥用药物一样与大脑中相同的阿片类受体相互作用。在这项研究中，我们报告了一种优化的双半抗原，用作免疫药物治疗工具，以开发能够与外周芬太尼污染的海洛因结合的抗体，从而阻止药物对中枢神经系统的精神作用。这种疫苗产生具有纳摩尔亲和力的抗体，并有效阻断掺假海洛因引起的阿片类镇痛作用。这些发现为针对阿片类药物使用障碍的广谱免疫药物疗法的化学连续半抗原的开发提供了进一步的见解。
Unintentional overdose deaths related to opioids and psychostimulants have increased in prevalence due to the adulteration of these drugs with fentanyl. Synergistic effects between illicit compounds and fentanyl cause aggravated respiratory depression, leading to inadvertent fatalities. Traditional small-molecule therapies implemented in the expanding opioid epidemic present numerous problems since they interact with the same opioid receptors in the brain as the abused drugs. In this study, we report an optimized dual hapten for use as an immunopharmacotherapeutic tool in order to develop antibodies capable of binding to fentanyl-contaminated heroin in the periphery, thus impeding the drugs’ psychoactive effects on the central nervous system. This vaccine produced antibodies with nanomolar affinities and effectively blocked opioid analgesic effects elicited by adulterated heroin. These findings provide further insight into the development of chemically contiguous haptens for broad-spectrum immunopharmacotherapies against opioid use disorders.