Developing a vaccine against multiple psychoactive targets: a case study of heroin.
Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. Currently approved heroin addiction medications include drugs that bind at the same receptors (e.g. opioid receptors) occupied by heroin and/or its metabolites in the brain, but undesired side effects of these treatments, maintenance dependence and relapse to drug taking remains problematic. A vaccine capable of blocking heroin's effects could provide an economical, long-lasting and sustainable adjunct to heroin addiction therapy without the side effects associated with available treatment options. Heroin, however, presents a particularly challenging vaccine target as it is metabolized to multiple psychoactive molecules of differing lipophilicity, with differing abilities to cross the blood brain barrier. In this review, we discuss the opiate scaffolding and hapten design considerations to confer immunogenicity as well as the specificity of the immune response towards structurally similar opiates. In addition, we detail different strategies employed in the design of immunoconjugates for a vaccine-based therapy for heroin addiction treatment.
Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology and Worm Institute of Research and Medicine (WIRM), The Scripps Research Institute, La Jolla, California 92037, USA.
G Neilm
GN
Stowe
Joel E
JE
Schlosburg
Leandro F
LF
Vendruscolo
Scott
S
Edwards
Kaushik K
KK
Misra
Gery
G
Schulteis
Joseph S
JS
Zakhari
George F
GF
Koob
Kim D
KD
Janda
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D003932:Heroin / Q000737:chemistry / Q000378:metabolism; D006556:Heroin Dependence / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011619:Psychotropic Drugs / Q000138:chemical synthesis / Q000627:therapeutic use; D014612:Vaccines / Q000138:chemical synthesis* / Q000276:immunology / Q000627:therapeutic use*
D018796:Immunoconjugates; D011619:Psychotropic Drugs; D014612:Vaccines; D003932:Heroin