Substance use disorders (SUD) present a worldwide challenge with few effective therapies except for the relative efficacy of opioid pharmacotherapies, despite limited treatment access. However, the proliferation of illicit fentanyl use initiated a dramatic and cascading epidemic of lethal overdoses. This rise in fentanyl overdoses regenerated an interest in vaccine immunotherapy, which, despite an optimistic start in animal models over the past 50 years, yielded disappointing results in human clinical trials of vaccines against nicotine, stimulants (cocaine and methamphetamine), and opioids. After a brief review of clinical and selected preclinical vaccine studies, the “lessons learned” from the previous vaccine clinical trials are summarized, and then the newest challenge of a vaccine against fentanyl and its analogs is explored. Animal studies have made significant advances in vaccine technology for SUD treatment over the past 50 years, and the resulting anti-fentanyl vaccines show remarkable promise for ending this epidemic of fentanyl deaths.

物质使用障碍（SUD）是一个世界性的挑战，尽管治疗手段有限，但除了阿片类药物疗法的相对疗效外，几乎没有有效的治疗方法。然而，芬太尼非法使用的激增引发了致命过量用药的戏剧性连锁流行。芬太尼过量服用的增加重新引起了人们对疫苗免疫疗法的兴趣，尽管过去 50 年在动物模型中的疫苗免疫疗法取得了乐观的开端，但在尼古丁、兴奋剂（可卡因和甲基苯丙胺）和阿片类药物疫苗的人体临床试验中却产生了令人失望的结果。在对临床和选定的临床前疫苗研究进行简要回顾后，总结了以往疫苗临床试验的“经验教训”，然后探讨了针对芬太尼及其类似物的疫苗的最新挑战。过去 50 年来，动物研究在 SUD 治疗疫苗技术方面取得了重大进展，由此产生的抗芬太尼疫苗显示出结束芬太尼死亡流行病的巨大希望。