title: Influencing Antibody-Mediated Attenuation of Methamphetamine CNS Distribution through Vaccine Linker Design.
abstract: Active vaccination examining a single hapten engendered with a series of peptidic linkers has resulted in the production of antimethamphetamine antibodies. Given the limited chemical complexity of methamphetamine, the structure of the linker species embedded within the hapten could have a substantial effect on the ultimate efficacy of the resulting vaccines. Herein, we investigate linker effects by generating a series of methamphetamine haptens that harbor a linker with varying amino acid identity, peptide length, and associated carrier protein. Independent changes in each of these parameters were found to result in alterations in both the quantity and quality of the antibodies induced by vaccination. Although it was found that the consequence of the linker design was also dependent on the identity of the carrier protein, we demonstrate overall that the inclusion of a short, structurally simple, amino acid linker benefits the efficacy of a methamphetamine vaccine in limiting brain penetration of the free drug.
authors.affiliation: Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Major
authors.initials: M
authors.lastname: Gooyit
authors.affiliation: Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Pedro O
authors.initials: PO
authors.lastname: Miranda
authors.affiliation: Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Cody J
authors.initials: CJ
authors.lastname: Wenthur
authors.affiliation: Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Ducime
authors.affiliation: Departments of Chemistry and Immunology and Microbial Science, The Skaggs Institute for Chemical Biology, and The Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Kim D
authors.identifier: 0000-0001-6759-4227
authors.initials: KD
authors.lastname: Janda
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D000906:Antibodies; D000915:Antibody Affinity; D000918:Antibody Specificity; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D004168:Diphtheria Toxoid / Q000737:chemistry / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D008694:Methamphetamine / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D011863:Radioimmunoassay
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000697:Central Nervous System Stimulants; D004168:Diphtheria Toxoid; D006241:Haptens; D008694:Methamphetamine
keywords: CNS distribution; Methamphetamine; antimethamphetamine antibody; hapten; linker design; vaccine