Eubanks Lisa M, Blake Steven, Natori Yoshihiro, Ellis Beverly, Bremer Paul T, Janda Kim D
Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, La Jolla, California 92037, United States.
ACS Chem Biol. 2021 Feb 19;16(2):277-282. doi: 10.1021/acschembio.1c00026. Epub 2021 Feb 3.
The opioid epidemic remains a dire public health crisis with millions of people currently suffering from opioid use disorder (OUD) and tens of thousands dying each year. Synthetic opioids are most responsible for the crisis because of their extreme potency and ease of manufacture. Carfentanil for example has an estimated potency 10,000 times greater than morphine and thus is highly dangerous for human use. Herein, we report two synthetic opioid vaccines that elicited high-affinity antibodies against carfentanil and fentanyl with cross-reactivity to other synthetic opioids in mice and offered protection against opioid-induced respiratory depression, the primary cause of overdose deaths. These vaccines also successfully diminished drug biodistribution to the brain and shielded against opioid analgesic effects. Collectively, these findings provide new insights into the development of immunotherapeutic strategies aimed at opioid abuse and overdose.
阿片类药物流行仍然是一场严峻的公共卫生危机，目前有数百万 人患有阿片类药物使用障碍（OUD），每年有 数万人死亡。合成阿片类药物对这场危机负有最大责任，因为它们效力极强且易于制造。例如，卡芬太尼的效力估计比吗啡大 10000 倍，因此对人类使用极具危险性。在此，我们报告了两种合成阿片类疫苗，它们在小鼠体内引发了针对卡芬太尼和芬太尼的高亲和力抗体，并与其他合成阿片类药物发生交叉反应，还提供了针对阿片类药物引起的呼吸抑制的保护作用，而呼吸抑制是过量用药死亡的主要原因。这些疫苗还成功减少了药物在大脑中的生物分布，并抵御了阿片类药物的镇痛作用。总的来说，这些发现为旨在解决阿片类药物滥用和过量用药问题的免疫治疗策略的开发提供了新的见解。
