title: A vaccine strategy that induces protective immunity against heroin.
abstract: Heroin addiction is a wide-reaching problem with a spectrum of damaging social consequences. A vaccine capable of blocking heroin's effects could provide a long-lasting and sustainable adjunct to heroin addiction therapy. Heroin, however, presents a particularly challenging immunotherapeutic target, as it is metabolized to multiple psychoactive molecules. To reconcile this dilemma, we examined the idea of a singular vaccine with the potential to display multiple drug-like antigens; thus two haptens were synthesized, one heroin-like and another morphine-like in chemical structure. A key feature in this approach is that immunopresentation with the heroin-like hapten is thought to be immunochemically dynamic such that multiple haptens are simultaneously presented to the immune system. We demonstrate the significance of this approach through the extremely rapid generation of robust polyclonal antibody titers with remarkable specificity. Importantly, both the antinociceptive effects of heroin and acquisition of heroin self-administration were blocked in rats vaccinated using the heroin-like hapten.
authors.affiliation: Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: G Neil
authors.initials: GN
authors.lastname: Stowe
authors.forename: Leandro F
authors.initials: LF
authors.lastname: Vendruscolo
authors.forename: Scott
authors.initials: S
authors.lastname: Edwards
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schlosburg
authors.forename: Kaushik K
authors.initials: KK
authors.lastname: Misra
authors.forename: Gery
authors.initials: G
authors.lastname: Schulteis
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Mayorov
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Zakhari
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D002417:Cattle; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens / Q000737:chemistry / Q000276:immunology; D006433:Hemocyanins / Q000737:chemistry; D003932:Heroin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006556:Heroin Dependence / Q000276:immunology / Q000517:prevention & control*; D006358:Hot Temperature; D018796:Immunoconjugates / Q000737:chemistry* / Q000276:immunology; D008297:Male; D015394:Molecular Structure; D009020:Morphine / Q000737:chemistry; D009294:Narcotics / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D055502:Secondary Prevention; D012646:Self Administration; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013329:Structure-Activity Relationship; D014110:Touch; D014612:Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology
chemical_list: D004337:Drug Carriers; D006241:Haptens; D018796:Immunoconjugates; D009294:Narcotics; D011619:Psychotropic Drugs; D014612:Vaccines; D012710:Serum Albumin, Bovine; D003932:Heroin; D009020:Morphine; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin