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Development of a Clinically Viable Heroin Vaccine

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Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, California 92037, United States
Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 N 12th Street, Richmond, Virginia 23298, United States
Cite this: J. Am. Chem. Soc. 2017, 139, 25, 8601–8611
Publication Date (Web):June 2, 2017
https://doi.org/10.1021/jacs.7b03334
Copyright © 2017 American Chemical Society

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    Abstract

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

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.7b03334.

    • Materials and methods, conjugate mass data, titer data, additional mouse and monkey vaccine data: Tables S1–S2, Figures S1–S10 (PDF)

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