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Research Article

Dynamic vaccine blocks relapse to compulsive intake of heroin

Joel E. Schlosburg, Leandro F. Vendruscolo, Paul T. Bremer, Jonathan W. Lockner, Carrie L. Wade, Ashlee A. K. Nunes, G. Neil Stowe, Scott Edwards, Kim D. Janda, and George F. Koob
PNAS first published May 6, 2013; https://doi.org/10.1073/pnas.1219159110
Joel E. Schlosburg
aCommittee on the Neurobiology of Addictive Disorders and
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  • For correspondence: schlos@scripps.edu
Leandro F. Vendruscolo
aCommittee on the Neurobiology of Addictive Disorders and
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Paul T. Bremer
bDepartments of Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
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Jonathan W. Lockner
bDepartments of Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
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Carrie L. Wade
aCommittee on the Neurobiology of Addictive Disorders and
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Ashlee A. K. Nunes
bDepartments of Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
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G. Neil Stowe
bDepartments of Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
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Scott Edwards
aCommittee on the Neurobiology of Addictive Disorders and
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Kim D. Janda
bDepartments of Chemistry, Immunology, and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
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George F. Koob
aCommittee on the Neurobiology of Addictive Disorders and
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  1. Edited by Richard D. Palmiter, University of Washington, Seattle, WA, and approved February 26, 2013 (received for review November 14, 2012)

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Abstract

Heroin addiction, a chronic relapsing disorder characterized by excessive drug taking and seeking, requires constant psychotherapeutic and pharmacotherapeutic interventions to minimize the potential for further abuse. Vaccine strategies against many drugs of abuse are being developed that generate antibodies that bind drug in the bloodstream, preventing entry into the brain and nullifying psychoactivity. However, this strategy is complicated by heroin’s rapid metabolism to 6-acetylmorphine and morphine. We recently developed a “dynamic” vaccine that creates antibodies against heroin and its psychoactive metabolites by presenting multihaptenic structures to the immune system that match heroin’s metabolism. The current study presents evidence of effective and continuous sequestration of brain-permeable constituents of heroin in the bloodstream following vaccination. The result is efficient blockade of heroin activity in treated rats, preventing various features of drugs of abuse: heroin reward, drug-induced reinstatement of drug seeking, and reescalation of compulsive heroin self-administration following abstinence in dependent rats. The dynamic vaccine shows the capability to significantly devalue the reinforcing and motivating properties of heroin, even in subjects with a history of dependence. In addition, targeting a less brain-permeable downstream metabolite, morphine, is insufficient to prevent heroin-induced activity in these models, suggesting that heroin and 6-acetylmorphine are critical players in heroin’s psychoactivity. Because the heroin vaccine does not target opioid receptors or common opioid pharmacotherapeutics, it can be used in conjunction with available treatment options. Thus, our vaccine represents a promising adjunct therapy for heroin addiction, providing continuous heroin antagonism, requiring minimal medical monitoring and patient compliance.

  • immunotherapy
  • antinociception
  • progressive ratio

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: schlos{at}scripps.edu.
  • Author contributions: J.E.S., L.F.V., C.L.W., G.N.S., S.E., K.D.J., and G.F.K. designed research; J.E.S., L.F.V., P.T.B., J.W.L., C.L.W., A.A.K.N., G.N.S., and S.E. performed research; P.T.B., A.A.K.N., G.N.S., and K.D.J. contributed new reagents/analytic tools; J.E.S., P.T.B., J.W.L., A.A.K.N., G.N.S., K.D.J., and G.F.K. analyzed data; and J.E.S. and G.F.K. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1219159110/-/DCSupplemental.

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Vaccine blocks relapse and compulsive heroin use
Joel E. Schlosburg, Leandro F. Vendruscolo, Paul T. Bremer, Jonathan W. Lockner, Carrie L. Wade, Ashlee A. K. Nunes, G. Neil Stowe, Scott Edwards, Kim D. Janda, George F. Koob
Proceedings of the National Academy of Sciences May 2013, 201219159; DOI: 10.1073/pnas.1219159110

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Vaccine blocks relapse and compulsive heroin use
Joel E. Schlosburg, Leandro F. Vendruscolo, Paul T. Bremer, Jonathan W. Lockner, Carrie L. Wade, Ashlee A. K. Nunes, G. Neil Stowe, Scott Edwards, Kim D. Janda, George F. Koob
Proceedings of the National Academy of Sciences May 2013, 201219159; DOI: 10.1073/pnas.1219159110
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