title: An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.
abstract: Prescription opioids (POs) such as oxycodone and hydrocodone are highly effective medications for pain management, yet they also present a substantial risk for abuse and addiction. The consumption of POs has been escalating worldwide, resulting in tens of thousands of deaths due to overdose each year. Pharmacokinetic strategies based upon vaccination present an attractive avenue to suppress PO abuse. Herein, the preparation of two active PO vaccines is described that were found to elicit high-affinity antiopioid antibodies through a structurally congruent drug-hapten design. Administration of these vaccines resulted in a significant blockade of opioid analgesic activity, along with an unprecedented increase in drug serum half-life and protection against lethal overdose.
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kimishima
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Cody J
authors.identifier: 0000-0001-6043-3842
authors.initials: CJ
authors.lastname: Wenthur
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , La Jolla, California 92037, United States.
authors.forename: Kim D
authors.identifier: 0000-0001-6759-4227
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D062787:Drug Overdose / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D006207:Half-Life; D006241:Haptens / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D051379:Mice; D009293:Opioid-Related Disorders / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D010098:Oxycodone / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000097:blood / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*
chemical_list: D000701:Analgesics, Opioid; D006241:Haptens; D013745:Tetanus Toxoid; D014612:Vaccines; D006853:Hydrocodone; D010098:Oxycodone