Substance use disorder, especially in relation to opioids such as heroin and fentanyl, is a significant public health issue and has intensified in recent years. As a result, substantial interest exists in developing therapeutics to counteract the effects of abused drugs. A promising universal strategy for antagonizing the pharmacology of virtually any drug involves the development of a conjugate vaccine, wherein a hapten structurally similar to the target drug is conjugated to an immunogenic carrier protein. When formulated with adjuvants and immunized, the immunoconjugate should elicit serum IgG antibodies with the ability to sequester the target drug to prevent its entry to the brain, thereby acting as an immunoantagonist. Despite the failures of first-generation conjugate vaccines against cocaine and nicotine in clinical trials, second-generation vaccines have shown dramatically improved performance in preclinical models, thus renewing the potential clinical utility of conjugate vaccines in curbing substance use disorder. This review explores the critical design elements of drug conjugate vaccines such as hapten structure, adjuvant formulation, bioconjugate chemistry, and carrier protein selection. Methods for evaluating these vaccines are discussed, and recent progress in vaccine development for each drug is summarized.

中文翻译：

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为物质使用障碍而进行疫苗免疫治疗。

物质使用障碍，特别是与诸如海洛因和芬太尼等阿片类药物有关的疾病，是一个重大的公共卫生问题，并且近年来已经加剧。结果，人们对开发治疗药物以抵消滥用药物的影响存在浓厚兴趣。对抗几乎任何药物的药理学的有前途的通用策略涉及缀合物疫苗的开发，其中结构类似于靶标药物的半抗原缀合至免疫原性载体蛋白。当与佐剂一起配制并进行免疫接种时，免疫偶联物应引起血清IgG抗体具有隔离目标药物的能力，以防止其进入大脑，从而起到免疫拮抗剂的作用。尽管第一代针对可卡因和尼古丁的结合疫苗在临床试验中失败了，第二代疫苗在临床前模型中已显示出显着改善的性能，从而更新了结合疫苗在遏制物质使用障碍方面的潜在临床效用。这篇综述探讨了药物结合疫苗的关键设计要素，例如半抗原结构，佐剂配方，生物结合化学和载体蛋白选择。讨论了评估这些疫苗的方法，并总结了每种药物在疫苗开发中的最新进展。和载体蛋白的选择。讨论了评估这些疫苗的方法，并总结了每种药物在疫苗开发中的最新进展。和载体蛋白的选择。讨论了评估这些疫苗的方法，并总结了每种药物在疫苗开发中的最新进展。