Conjugate Vaccine Immunotherapy for Substance Use Disorder.

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.