Development of a Clinically Viable Heroin Vaccine

• DOI: 10.1021/jacs.7b03334
• Publication Date: 2017-06-02T17:24:13Z
• Authors: Paul T. Bremer; Joel E. Schlosburg; Matthew L. Banks; Floyd. F. Steele; Bin Zhou; Justin L. Poklis; Kim D. Janda
• Keywords: Heroin dependence

Heroin is a highly abused opioid and incurs significant detriment to society worldwide. In an effort expand the limited pharmacotherapy options for use disorders, heroin conjugate vaccine was developed through comprehensive evaluation of hapten structure, carrier protein, adjuvant dosing. Immunization mice with optimized heroin-tetanus toxoid (TT) formulated adjuvants alum CpG oligodeoxynucleotide (ODN) generated "immunoantagonism", reducing potency by >15-fold. Moreover, effects proved be durable, persisting over eight months. The lead effective in rhesus monkeys, generating sustained antidrug IgG titers each subject. Characterization both mouse monkey antiheroin antibodies surface plasmon resonance (SPR) revealed low nanomolar antiserum affinity key metabolite, 6-acetylmorphine (6AM), minimal cross reactivity clinically used opioids. Following series challenges six months vaccinated drug-sequestering caused marked attenuation (>4-fold) schedule-controlled responding (SCR) behavioral assay. Overall, these preclinical results provide empirical foundation supporting further potential clinical utility treating disorders.