Therapeutic and Prophylactic Vaccines to Counteract Fentanyl Use Disorders and Toxicity.
Therapeutic and Prophylactic Vaccines to Counteract Fentanyl Use Disorders and Toxicity.
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DOI：
10.1021/acs.jmedchem.0c01042
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发表时间：
2020-12-10
影响因子：
7.3
通讯作者：
Pravetoni M
中科院分区：
文献类型：
--
作者：
Robinson C;Gradinati V;Hamid F;Baehr C;Crouse B;Averick S;Kovaliov M;Harris D;Runyon S;Baruffaldi F;LeSage M;Comer S;Pravetoni M
由于非法芬太尼及其强效类似物的广泛使用，全世界致命过量的发生率有所增加。疫苗提供了一种有希望的策略，以减少阿片类药物使用障碍（OUD）的患病率，并防止意外和故意暴露于芬太尼及其衍生物的毒性。本研究描述了由与载体蛋白缀合的新型芬太尼基半抗原组成的疫苗制剂的开发和表征。在用芬太尼及其类似物攻击的小鼠和大鼠中测试疫苗针对阿片样物质诱导的行为和毒性的效力。预防性疫苗接种减少芬太尼和舒芬太尼诱导的抗伤害，呼吸抑制和心动过缓的小鼠和大鼠。治疗性疫苗接种也减少了大鼠静脉内芬太尼自我给药。由于其选择性，疫苗不会干扰常用麻醉剂的药理作用，也不会干扰美沙酮、纳洛酮、羟考酮或海洛因。这些临床前数据支持将疫苗转化为对抗芬太尼使用障碍和毒性的可行策略。
The incidence of fatal overdoses has increased worldwide due to the widespread access to illicit fentanyl and its potent analogues. Vaccines offer a promising strategy to reduce the prevalence of opioid use disorders (OUDs) and to prevent toxicity from accidental and deliberate exposure to fentanyl and its derivatives. This study describes the development and characterization of vaccine formulations consisting of novel fentanyl-based haptens conjugated to carrier proteins. Vaccine efficacy was tested against opioid-induced behavior and toxicity in mice and rats challenged with fentanyl and its analogues. Prophylactic vaccination reduced fentanyl- and sufentanil-induced antinociception, respiratory depression, and bradycardia in mice and rats. Therapeutic vaccination also reduced fentanyl intravenous self-administration in rats. Because of their selectivity, vaccines did not interfere with the pharmacological effects of commonly used anesthetics nor with methadone, naloxone, oxycodone, or heroin. These preclinical data support the translation of vaccines as a viable strategy to counteract fentanyl use disorders and toxicity.
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