The ongoing opioid crisis, now into its second decade, represents a global public health challenge. Moreover, the opioid crisis has manifested despite clinical access to three approved opioid use disorder medications: the full opioid agonist methadone, the partial opioid agonist buprenorphine, and the opioid antagonist naltrexone. Although current opioid use disorder medications are underutilized, the ongoing opioid crisis has also identified the need for basic research to develop both safer and more effective opioid use disorder medications. Emerging preclinical evidence suggests that opioid-targeted vaccines or immunopharmacotherapies may be promising opioid use disorder therapeutics. One premise for this article is to critically examine whether vaccine effectiveness evaluated using preclinical antinociceptive endpoints is predictive of vaccine effectiveness on abuse-related endpoints such as drug self-administration, drug discrimination, and conditioned place preference. A second premise is to apply decades of knowledge in the preclinical evaluation of candidate small-molecule therapeutics for opioid use disorder to the preclinical evaluation of candidate opioid use disorder immunopharmacotherapies. We conclude with preclinical experimental design attributes to enhance preclinical-to-clinical translatability and potential future directions for immunopharmacotherapies to address the dynamic illicit opioid environment.

持续存在的阿片类药物危机现已进入第二个十年，代表着全球公共卫生挑战。此外，尽管临床上可以使用三种已批准的阿片类药物使用障碍药物：完全阿片类药物激动剂美沙酮、部分阿片类药物激动剂丁丙诺啡和阿片类药物拮抗剂纳曲酮，但阿片类药物危机已经显现。尽管目前的阿片类药物使用障碍药物尚未得到充分利用，但持续的阿片类药物危机也表明需要进行基础研究来开发更安全、更有效的阿片类药物使用障碍药物。新出现的临床前证据表明，阿片类药物靶向疫苗或免疫药物疗法可能是有前途的阿片类药物使用障碍治疗方法。本文的一个前提是批判性地研究使用临床前抗伤害终点评估的疫苗有效性是否可以预测疫苗对滥用相关终点（例如药物自我给药、药物歧视和条件性位置偏好）的有效性。第二个前提是将几十年来阿片类药物使用障碍候选小分子疗法的临床前评估知识应用于候选阿片类药物使用障碍免疫药物疗法的临床前评估。我们总结了临床前实验设计的属性，以增强临床前到临床的可转化性，以及免疫药物疗法解决动态非法阿片类药物环境的潜在未来方向。