Global estimates suggest that there are over 14 million heroin users and that approximately 10% of all new HIV infections can be attributed to injection drug users (IDUs). Based on IDUs the HIV epidemic can be viewed as being largely driven by injection drug use in many regions of the world. Undeniably HIV prevalence related to intravenous drug use has risen dramatically in Eastern Europe, Asia, Iran, North Africa, and in Latin America. It has been noted that there is less than 20% coverage of the IDUs who receive HIV treatment and care in Eastern Europe and central Asia, where opiate abuse is central to the expanding epidemic. To exacerbate the situation, policies in developing countries still prohibit substitution therapy with buprenorphine or methadone. Furthermore, many IDUs are routinely excluded from HIV treatment and care;accordingly, this population has a higher incidence of AIDS-related mortality. Reasons for this lack of treatment include such elements as confusion concerning the impact of heroin abuse, the spread of HIV and a lack of infrastructure or denial of the basic replacement therapies such as methadone that could facilitate HIV treatment. Studies have shown difficulties IDUs have in accessing and/or remaining in HIV care as well as the potential for overcoming their own obstacles through treatment of substance abuse by supervised medical personnel. In these regards our proposal seeks to develop methods that can be long acting, sustainable therapies for opiate addiction. In particular the development of heroin/morphine protein conjugates, termed heroin/morphine conjugate vaccines (HCVs), will be advanced in the hopes to reduce opiate abuse and thus the spread of HIV.
The specific aims of our proposal are: (1) To design and synthesize haptens for use in the development of HCVs.(2) To determine the optimal protein carrier and adjuvant for the development of high antibody titers against the heroin conjugate vaccines. (3) To examine alterations in the pharmacokinetics of heroin provided by HCV candidates in rats. (4) To determine the behavioral effects in rats of the most promising HCV in a model of heroin self-administration and reinstatement in dependent rats. Successful completion of these studies could provide an alternative strategy for treatment of opiate addiction and also for HIV prevention.

Public Health Relevance

There are over 14 million heroin users and that approximately 10% of all new HIV infections can be attributed to injection drug users. Thus, there is an urgent need to develop therapies for the treatment of heroin addiction and for HIV prevention. Our goals are to develop vaccines as therapeutics for the treatment of opiate addiction, which if successful could reduce risk for the acquisition and transmission of HIV.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Special Emphasis Panel (ZRG1-MDCN-C (91))
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Chiang, Nora
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Scripps Research Institute
La Jolla
United States
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Bremer, Paul T; Janda, Kim D (2017) Conjugate Vaccine Immunotherapy for Substance Use Disorder. Pharmacol Rev 69:298-315
Bremer, Paul T; Schlosburg, Joel E; Banks, Matthew L et al. (2017) Development of a Clinically Viable Heroin Vaccine. J Am Chem Soc 139:8601-8611
Collins, K C; Schlosburg, J E; Lockner, J W et al. (2014) Lipid tucaresol as an adjuvant for methamphetamine vaccine development. Chem Commun (Camb) 50:4079-81
Collins, Karen C; Janda, Kim D (2014) Investigating hapten clustering as a strategy to enhance vaccines against drugs of abuse. Bioconjug Chem 25:593-600
Bremer, Paul T; Schlosburg, Joel E; Lively, Jenny M et al. (2014) Injection route and TLR9 agonist addition significantly impact heroin vaccine efficacy. Mol Pharm 11:1075-80
Matyas, Gary R; Mayorov, Alexander V; Rice, Kenner C et al. (2013) Liposomes containing monophosphoryl lipid A: a potent adjuvant system for inducing antibodies to heroin hapten analogs. Vaccine 31:2804-10
Schlosburg, Joel E; Vendruscolo, Leandro F; Bremer, Paul T et al. (2013) Dynamic vaccine blocks relapse to compulsive intake of heroin. Proc Natl Acad Sci U S A 110:9036-41
Bremer, Paul T; Janda, Kim D (2012) Investigating the effects of a hydrolytically stable hapten and a Th1 adjuvant on heroin vaccine performance. J Med Chem 55:10776-80
Stowe, G Neil; Janda, Kim D (2011) A Diels-Alder Reaction Conducted Within the Parameters of Aqueous Organocatalysis: Still Just Smoke and Mirrors. Tetrahedron Lett 52:2085-2087
Stowe, G Neil; Vendruscolo, Leandro F; Edwards, Scott et al. (2011) A vaccine strategy that induces protective immunity against heroin. J Med Chem 54:5195-204

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