A Vaccine Strategy that Induces Protective Immunity against Heroin

作者：Stowe G Neil; Vendruscolo Leandro F; Edwards Scott; Schlo**urg Joel E; Misra Kaushik K; Schulteis Gery; Mayorov Alexander V; Zakhari Joseph S; Koob George F; Janda Kim D^*

来源：Journal of Medicinal Chemistry, 2011, 54(14): 5195-5204.

DOI：10.1021/jm200461m

Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma, we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.

• 出版日期2011-7-28