title: Probing active cocaine vaccination performance through catalytic and noncatalytic hapten design.
abstract: Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complementary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH (keyhole limpet hemocyannin) was found to elicit persistent high-titer, cocaine-specific antibodies and blunt cocaine-induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges, the vaccine's protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse.
authors.affiliation: Departments of Chemistry and Immunology, The Skaggs Institute for Chemical Biology, The Worm Institute of Research and Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Cai
authors.forename: Timothy
authors.initials: T
authors.lastname: Whitfield
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hixon
authors.forename: Yanabel
authors.initials: Y
authors.lastname: Grant
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity; D055162:Biocatalysis; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015195:Drug Design; D006241:Haptens / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D018796:Immunoconjugates / Q000276:immunology / Q000494:pharmacology; D007700:Kinetics; D008124:Locomotion / Q000187:drug effects; D051379:Mice; D014611:Vaccination
chemical_list: D000906:Antibodies; D006241:Haptens; D018796:Immunoconjugates; D003042:Cocaine