Departments of Chemistry, Immunology and Microbial Science, Skaggs Institute for Chemical Biology , The Scripps Research Institute , La Jolla , California 92037 , United States.
ACS Chem Neurosci. 2018 Jun 20;9(6):1269-1275. doi: 10.1021/acschemneuro.8b00079. Epub 2018 Mar 23.
The sharp increase in overdose deaths involving illicit opioid use has been declared a national crisis in the United States. This growing number of overdose deaths can in part be attributed to the increased frequency of fentanyl contamination in the United States heroin supply. To combat this growing trend, we designed a vaccine containing a mixture of heroin and fentanyl hapten-conjugates as a proof-of-concept immunotherapy targeting a combination of these drugs. Rodents immunized with the admixture vaccine showed drug retention in serum and reduced distribution in the brain after administration of an intravenous bolus of heroin coadministered with fentanyl (10% w/w). Moreover, the admixture vaccine performed as well as or better than individual immunoconjugate vaccines in antinociception behavioral models and recognized six other fentanyl analogues with nanomolar affinity. Taken together, these data highlight the potential of an admixture vaccine against heroin contaminated with fentanyl.
在美国,非法阿片类药物使用导致的过量死亡人数急剧增加,已被宣布为全国性危机。过量死亡人数的增加在一定程度上可归因于美国海洛因供应中芬太尼污染的频率增加。为了应对这一日益增长的趋势,我们设计了一种疫苗,其中包含海洛因和芬太尼半抗原缀合物的混合物,作为针对这些药物组合的概念验证免疫疗法。用混合物疫苗免疫的啮齿动物在静脉推注海洛因和芬太尼(10%w/w)共给药后,血清中保留了药物,并且在大脑中的分布减少。此外,混合物疫苗在抗伤害行为模型中的效果与或优于单个免疫缀合物疫苗,并且能识别出其他 6 种具有纳摩尔亲和力的芬太尼类似物。总之,这些数据突出了针对被芬太尼污染的海洛因的混合物疫苗的潜力。