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Hapten Design for Anti-addiction Vaccine Development

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Biologics to Treat Substance Use Disorders

Abstract

The key scientific challenge in the emerging field of drugs of abuse vaccines is the delineation of the complex factors that determine the immune response to the target drug following administration with a chosen hapten. A concise summary is presented of all the various elements of hapten design for the four major drugs of abuse, along with comparative analysis of their relevance and strategic importance using the results of published immunization studies. The central theme is the difficulty in identifying robust, transferable strategies to increase vaccine efficacy given the inter-study variability in experimental factors that would ideally be standardized across the field. Nonetheless, advances made both rationally and empirically in hapten and vaccine design are progressing towards the efficacious treatment of addiction.

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References

  • Agard NJ, Prescher JA, Bertozzi CR. A strain-promoted [3 + 2] azide − alkyne cycloaddition for covalent modification of biomolecules in living systems. J Am Chem Soc. 2004;126(46):15046–7. doi:10.1021/ja044996f.

    Article  CAS  PubMed  Google Scholar 

  • Ambre J, Ruo TI, Nelson J, Belknap S. Urinary excretion of cocaine, benzoylecgonine, and ecgonine methyl ester in humans. J Anal Toxicol. 1988;12(6):301–6. doi:10.1093/jat/12.6.301.

    Article  CAS  PubMed  Google Scholar 

  • Andrews NJ, Waight PA, George RC, Slack MPE, Miller E. Impact and effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive pneumococcal disease in the elderly in England and wales. Vaccine. 2012;30(48):6802–8. doi:10.1016/j.vaccine.2012.09.019.

    Article  PubMed  Google Scholar 

  • Barceloux DG. Amphetamine and methamphetamine. In: Medical toxicology of drug abuse. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2012. p. 1–56. doi:10.1002/9781118105955.ch1.

  • Berzofsky JA, Schechter AN. The concepts of crossreactivity and specificity in immunology. Mol Immunol. 1981;18(8):751–63. doi:10.1016/0161-5890(81)90067-5.

    Article  CAS  PubMed  Google Scholar 

  • Bremer PT, Janda KD. Investigating the effects of a hydrolytically stable hapten and a Th1 adjuvant on heroin vaccine performance. J Med Chem. 2012;55(23):10776–80. doi:10.1021/jm301262z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brust JCM. Chapter 5 – cocaine. In: Brust JCM, editor. Neurological aspects of substance abuse. 2nd ed. Philadelphia: Butterworth-Heinemann; 2004. p. 139–99. doi:10.1016/B978-0-7506-7313-6.50009-X.

    Chapter  Google Scholar 

  • Buskas T, Thompson P, Boons G-J. Immunotherapy for cancer: synthetic carbohydrate-based vaccines. Chem Commun. 2009;36:5335–49.

    Article  CAS  Google Scholar 

  • Byrnes-Blake KA, Carroll FI, Abraham P, Owens SM. Generation of anti-(+)methamphetamine antibodies is not impeded by (+)methamphetamine administration during active immunization of rats. Int Immunopharmacol. 2001;1(2):329–38.

    Article  CAS  PubMed  Google Scholar 

  • Cai X, Tsuchikama K, Janda KD. Modulating cocaine vaccine potency through hapten fluorination. J Am Chem Soc. 2013a;135(8):2971–4. doi:10.1021/ja400356g.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai X, Whitfield T, Hixon MS, Grant Y, Koob GF, Janda KD. Probing active cocaine vaccination performance through catalytic and noncatalytic hapten design. J Med Chem. 2013b;56(9):3701–9. doi:10.1021/jm400228w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai X, Whitfield T, Moreno AY, Grant Y, Hixon MS, Koob GF, Janda KD. Probing the effects of hapten stability on cocaine vaccine immunogenicity. Mol Pharm. 2013c;10(11):4176–84. doi:10.1021/mp400214w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carrera MRA, Ashley JA, Parsons LH, Wirsching P, Koob GF, Janda KD. Suppression of psychoactive effects of cocaine by active immunization. Nature. 1995;378(6558):727–30.

    Article  CAS  PubMed  Google Scholar 

  • Carrera MRA, Ashley JA, Zhou B, Wirsching P, Koob GF, Janda KD. Cocaine vaccines: antibody protection against relapse in a rat model. Proc Natl Acad Sci. 2000;97(11):6202–6. doi:10.1073/pnas.97.11.6202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carrera MRA, Ashley JA, Wirsching P, Koob GF, Janda KD. A second-generation vaccine protects against the psychoactive effects of cocaine. Proc Natl Acad Sci U S A. 2001;98(4):1988–92. doi:10.1073/pnas.98.4.1988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carroll FI, Blough BE, Pidaparthi RR, Abraham P, Gong PK, Deng L, Huang X, Gunnell M, Lay JO, Peterson EC, Owens SM. Synthesis of mercapto-(+)-methamphetamine haptens and their use for obtaining improved epitope density on (+)-methamphetamine conjugate vaccines. J Med Chem. 2011;54(14):5221–8. doi:10.1021/jm2004943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cerny EH, Lévy R, Mauel J, Mpandi M, Mutter M, Henzelin-Nkubana C, Patiny L, Tuchscherer G, Cerny T. Preclinical development of a vaccine ‘against smoking’. Onkologie. 2002;25(5):406–11.

    CAS  PubMed  Google Scholar 

  • Chandrakumar NS, Carron CP, Meyer DM, Beardsley PM, Nash SA, Tam LL, Rafferty M. Phenylphosphonate monoester analogs of cocaine. Potential haptens for the generation of catalytic antibodies. Bioorg Med Chem Lett. 1993;3(2):309–12. doi:10.1016/S0960-894X(01)80899-4.

    Article  CAS  Google Scholar 

  • Chang C-eA, Chen W, Gilson MK. Ligand configurational entropy and protein binding. Proc Natl Acad Sci. 2007;104(5):1534–9. doi:10.1073/pnas.0610494104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collins KC, Janda KD. Investigating hapten clustering as a strategy to enhance vaccines against drugs of abuse. Bioconjug Chem. 2014;25(3):593–600. doi:10.1021/bc500016k.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collins KC, Schlosburg JE, Lockner JW, Bremer PT, Ellis BA, Janda KD. Lipid tucaresol as an adjuvant for methamphetamine vaccine development. Chem Commun. 2014;50(31):4079–81. doi:10.1039/c4cc00682h.

    Article  CAS  Google Scholar 

  • Cook CE, Jeffcoat AR, Hill JM, Pugh DE, Patetta PK, Sadler BM, White WR, Perez-Reyes M. Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos. 1993;21(4):717–23.

    CAS  PubMed  Google Scholar 

  • Cornish KE, de Villiers SHL, Pravetoni M, Pentel PR. Immunogenicity of individual vaccine components in a bivalent nicotine vaccine differ according to vaccine formulation and administration conditions. PLoS One. 2013;8(12), e82557. doi:10.1371/journal.pone.0082557.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cornuz J, Zwahlen S, Jungi WF, Osterwalder J, Klingler K, van Melle G, Bangala Y, Guessous I, Müller P, Willers J, Maurer P, Bachmann MF, Cerny T. A vaccine against nicotine for smoking cessation: a randomized controlled trial. PLoS One. 2008;3(6), e2547.

    Article  PubMed  PubMed Central  Google Scholar 

  • de Villiers SHL, Lindblom N, Kalayanov G, Gordon S, Malmerfelt A, Johansson AM, Svensson TH. Active immunization against nicotine suppresses nicotine-induced dopamine release in the rat nucleus accumbens shell. Respiration. 2002;69(3):247–53.

    Article  PubMed  Google Scholar 

  • de Villiers SHL, Lindblom N, Kalayanov G, Gordon S, Baraznenok I, Malmerfelt A, Marcus MM, Johansson AM, Svensson TH. Nicotine hapten structure, antibody selectivity and effect relationships: results from a nicotine vaccine screening procedure. Vaccine. 2010;28(10):2161–8. doi:10.1016/j.vaccine.2009.12.051.

    Article  PubMed  CAS  Google Scholar 

  • de Villiers SHL, Cornish KE, Troska AJ, Pravetoni M, Pentel PR. Increased efficacy of a trivalent nicotine vaccine compared to a dose-matched monovalent vaccine when formulated with alum. Vaccine. 2013;31(52):6185–93. doi:10.1016/j.vaccine.2013.10.051.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • DeTar DF, Silverstein R. Reactions of carbodiimides. I. The mechanisms of the reactions of acetic acid with dicyclohexylcarbodiimide1,2. J Am Chem Soc. 1966;88(5):1013–9. doi:10.1021/ja00957a027.

    Article  CAS  Google Scholar 

  • Duncan RJS, Weston PD, Wrigglesworth R. A new reagent which may be used to introduce sulfhydryl groups into proteins, and its use in the preparation of conjugates for immunoassay. Anal Biochem. 1983;132(1):68–73. doi:10.1016/0003-2697(83)90426-8.

    Article  CAS  PubMed  Google Scholar 

  • Duryee MJ, Bevins RA, Reichel CM, Murray JE, Dong Y, Thiele GM, Sanderson SD. Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines. Vaccine. 2009;27(22):2981–8.

    Article  CAS  PubMed  Google Scholar 

  • Dwoskin LP, Teng L, Buxton ST, Crooks PA. (S)-(−)-cotinine, the major brain metabolite of nicotine, stimulates nicotinic receptors to evoke [3H]dopamine release from rat striatal slices in a calcium-dependent manner. J Pharmacol Exp Ther. 1999;288(3):905–11.

    CAS  PubMed  Google Scholar 

  • Fontaine SD, Reid R, Robinson L, Ashley GW, Santi DV. Long-term stabilization of maleimide–thiol conjugates. Bioconjug Chem. 2014;26(1):145–52. doi:10.1021/bc5005262.

    Article  PubMed  CAS  Google Scholar 

  • Fox BS, Kantak KM, Edwards MA, Black KM, Bollinger BK, Botka AJ, French TL, Thompson TL, Schad VC, Greenstein JL, Gefter ML, Exley MA, Swain PA, Briner TJ. Efficacy of a therapeutic cocaine vaccine in rodent models. Nat Med. 1996;2(10):1129–32.

    Article  CAS  PubMed  Google Scholar 

  • Gómez-Nuñez M, Haro KJ, Dao T, Chau D, Won A, Escobar-Alvarez S, Zakhaleva V, Korontsvit T, Gin DY, Scheinberg DA. Non-natural and photo-reactive amino acids as biochemical probes of immune function. PLoS One. 2008;3(12), e3938.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grandjean C, Boutonnier A, Guerreiro C, Fournier J-M, Mulard LA. On the preparation of carbohydrate − protein conjugates using the traceless Staudinger ligation. J Org Chem. 2005;70(18):7123–32. doi:10.1021/jo0505472.

    Article  CAS  PubMed  Google Scholar 

  • Haney M, Gunderson EW, Jiang H, Collins ED, Foltin RW. Cocaine-specific antibodies blunt the subjective effects of smoked cocaine in humans. Biol Psychiatry. 2010;67(1):59–65. doi:10.1016/j.biopsych.2009.08.031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hatsukami DK, Grillo M, Pentel PR, Oncken C, Bliss R. Safety of cotinine in humans: physiologic, subjective, and cognitive effects. Pharmacol Biochem Behav. 1997;57(4):643–50. doi:10.1016/S0091-3057(97)80001-9.

    Article  CAS  PubMed  Google Scholar 

  • Hatsukami DK, Rennard S, Jorenby D, Fiore M, Koopmeiners J, de Vos A, Horwith G, Pentel PR. Safety and immunogenicity of a nicotine conjugate vaccine in current smokers. Clin Pharmacol Ther. 2005;78(5):456–67. doi:10.1016/j.clpt.2005.08.007.

    Article  CAS  PubMed  Google Scholar 

  • Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA, Tashkin DP, Reus VI, Akhavain RC, Fahim REF, Kessler PD, Niknian M, Kalnik MW, Rennard SI. Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic. Clin Pharmacol Ther. 2011;89(3):392–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hieda Y, Keyler DE, Vandevoort JT, Kane JK, Ross CA, Raphael DE, Niedbalas RS, Pentel PR. Active immunization alters the plasma nicotine concentration in rats. J Pharmacol Exp Ther. 1997;283(3):1076–81.

    CAS  PubMed  Google Scholar 

  • Hieda Y, Keyler DE, Vandevoort JT, Niedbalas RS, Raphael DE, Ross CA, Pentel PR. Immunization of rats reduces nicotine distribution to brain. Psychopharmacology (Berl). 1999;143(2):150–7.

    Article  CAS  Google Scholar 

  • Hieda Y, Keyler DE, Ennifar S, Fattom A, Pentel PR. Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nicotine distribution to brain. Int J Immunopharmacol. 2000;22(10):809–19. doi:10.1016/S0192-0561(00)00042-4.

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann-Röder A, Kaiser A, Wagner S, Gaidzik N, Kowalczyk D, Westerlind U, Gerlitzki B, Schmitt E, Kunz H. Synthetic antitumor vaccines from tetanus toxoid conjugates of MUC1 glycopeptides with the thomsen–friedenreich antigen and a fluorine-substituted analogue. Angew Chem Int Ed. 2010;49(45):8498–503. doi:10.1002/anie.201003810.

    Article  CAS  Google Scholar 

  • Hukkanen J, Jacob P, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57(1):79–115. doi:10.1124/pr.57.1.3.

    Article  CAS  PubMed  Google Scholar 

  • Inturrisi CE, Schultz M, Shin S, Umans JG, Angel L, Simon EJ. Evidence from opiate binding studies that heroin acts through its metabolites. Life Sci. 1983;33:773–6. doi:10.1016/0024-3205(83)90616-1.

    Article  CAS  PubMed  Google Scholar 

  • Isomura S, Wirsching P, Janda KD. An immunotherapeutic program for the treatment of nicotine addiction: hapten design and synthesis. J Org Chem. 2001;66(12):4115–21. doi:10.1021/jo001442w.

    Article  CAS  PubMed  Google Scholar 

  • Janda KD, Treweek JB. Vaccines targeting drugs of abuse: is the glass half-empty or half-full? Nat Rev Immunol. 2012;12(1):67–72.

    CAS  Google Scholar 

  • Jeffcoat AR, Perez-Reyes M, Hill JM, Sadler BM, Cook CE. Cocaine disposition in humans after intravenous injection, nasal insufflation (snorting), or smoking. Drug Metab Dispos. 1989;17(2):153–9.

    CAS  PubMed  Google Scholar 

  • Jufer RA, Wstadik A, Walsh SL, Levine BS, Cone EJ. Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers. J Anal Toxicol. 2000;24(7):467–77. doi:10.1093/jat/24.7.467.

    Article  CAS  PubMed  Google Scholar 

  • Keenan RM, Hatsukami DK, Pentel PR, Thompson TN, Grillo MA. Pharmacodynamic effects of cotinine in abstinent cigarette smokers. Clin Pharmacol Ther. 1994;55(5):581–90. doi:10.1038/clpt.1994.72.

    Article  CAS  PubMed  Google Scholar 

  • Keyler DE, Roiko SA, Earley CA, Murtaugh MP, Pentel PR. Enhanced immunogenicity of a bivalent nicotine vaccine. Int Immunopharmacol. 2008;8(11):1589–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim Pei L, Smith MT. The antinociceptive potencies of oxycodone, noroxycodone and morphine after intracerebroventricular administration to rats. Life Sci. 1994;54(17):1229–36. doi:10.1016/0024-3205(94)00849-3.

    Article  Google Scholar 

  • Kolbrich EA, Barnes AJ, Gorelick DA, Boyd SJ, Cone EJ, Huestis MA. Major and minor metabolites of cocaine in human plasma following controlled subcutaneous cocaine administration. J Anal Toxicol. 2006;30(8):501–10. doi:10.1093/jat/30.8.501.

    Article  CAS  PubMed  Google Scholar 

  • Kosten TR, Biegel D. Therapeutic vaccines for substance dependence. Expert Rev Vaccines. 2002;1(3):365–71. doi:10.1586/14760584.1.3.365.

    Article  Google Scholar 

  • Kubler-Kielb J, Liu T-Y, Mocca C, Majadly F, Robbins JB, Schneerson R. Additional conjugation methods and immunogenicity of bacillus anthracis poly-γ-d-glutamic acid-protein conjugates. Infect Immun. 2006;74(8):4744–9. doi:10.1128/iai.00315-06.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuczenski R, Segal DS, Cho AK, Melega W. Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. J Neurosci. 1995;15(2):1308–17.

    CAS  PubMed  Google Scholar 

  • Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen L-Y, Shen DD. Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clin Pharmacol Ther. 2006;79(5):461–79. doi:10.1016/j.clpt.2006.01.009.

    Article  CAS  PubMed  Google Scholar 

  • Landry D, Zhao K, Yang G, Glickman M, Georgiadis T. Antibody-catalyzed degradation of cocaine. Science. 1993;259(5103):1899–901. doi:10.1126/science.8456315.

    Article  CAS  PubMed  Google Scholar 

  • Landsteiner K, van der Scheer J. Serological differentiation of steric isomers. J Exp Med. 1928;48(3):315–20. doi:10.1084/jem.48.3.315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langman RE. The specificity of immunological reactions. Mol Immunol. 2000;37(10):555–61. doi:10.1016/S0161-5890(00)00083-3.

    Article  CAS  PubMed  Google Scholar 

  • Langone JJ, Gjika HB, Van Vunakis H. Nicotine and its metabolites. Radioimmunoassays for nicotine and cotinine. Biochemistry. 1973;12(24):5025–30.

    Article  CAS  PubMed  Google Scholar 

  • LeSage MG, Pentel PR. Vaccines and drug-specific antibodies. In: Stolerman I, editor. Encyclopedia of psychopharmacology. Berlin/Heidelberg: Springer; 2010. p. 1355–7. doi:10.1007/978-3-540-68706-1_356.

    Google Scholar 

  • Li P, Zhao K, Deng S, Landry DW. Nonenzymatic hydrolysis of cocaine via intramolecular acid catalysis. Helv Chim Acta. 1999;82(1):85–9. doi:10.1002/(SICI)1522-2675(19990113)82:1<85::AID-HLCA85>3.0.CO;2-Q.

    Article  CAS  Google Scholar 

  • Li F, Cheng K, Antoline JFG, Iyer MR, Matyas GR, Torres OB, Jalah R, Beck Z, Alving CR, Parrish DA, Deschamps JR, Jacobson AE, Rice KC. Synthesis and immunological effects of heroin vaccines. Org Biomol Chem. 2014;12:7211. doi:10.1039/C4OB01053A.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lockner JW, Lively JM, Collins KC, Vendruscolo JCM, Azar MR, Janda KD. A conjugate vaccine using enantiopure hapten imparts superior nicotine-binding capacity. J Med Chem. 2015;58:1005–11. doi:10.1021/jm501625j.

    Article  CAS  PubMed  Google Scholar 

  • Marco M-P, Gee S, Hammock BD. Immunochemical techniques for environmental analysis II. Antibody production and immunoassay development. TrAC-Trends Anal Chem. 1995;14(8):415–25. doi:10.1016/0165-9936(95)90920-I.

    Article  CAS  Google Scholar 

  • Martell BA, Mitchell E, Poling J, Gonsai K, Kosten TR. Vaccine pharmacotherapy for the treatment of cocaine dependence. Biol Psychiatry. 2005;58(2):158–64. doi:10.1016/j.biopsych.2005.04.032.

    Article  CAS  PubMed  Google Scholar 

  • Martell BA, Orson FM, Poling J, Mitchell E, Rossen RD, Tracie G, Kosten TR. Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Arch Gen Psychiatry. 2009;66(10):1116–23. doi:10.1001/archgenpsychiatry.2009.128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsushita M, Hoffman TZ, Ashley JA, Zhou B, Wirsching P, Janda KD. Cocaine catalytic antibodies: the primary importance of linker effects. Bioorg Med Chem Lett. 2001;11(2):87–90. doi:10.1016/S0960-894X(00)00659-4.

    Article  CAS  PubMed  Google Scholar 

  • Matyas GR, Rice KC, Cheng K, Li F, Antoline JFG, Iyer MR, Jacobson AE, Mayorov AV, Beck Z, Torres OB, Alving CR. Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine. Vaccine. 2014;32(13):1473–9. doi:10.1016/j.vaccine.2014.01.028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maurer P, Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Müller P, Bachmann MF. A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity. Eur J Immunol. 2005;35(7):2031–40. doi:10.1002/eji.200526285.

    Article  CAS  PubMed  Google Scholar 

  • McCance EF, Price LH, Kosten TR, Jatlow PI. Cocaethylene: pharmacology, physiology and behavioral effects in humans. J Pharmacol Exp Ther. 1995;274(1):215–23.

    CAS  PubMed  Google Scholar 

  • Meijler MM, Matsushita M, Altobell LJ, Wirsching P, Janda KD. A new strategy for improved nicotine vaccines using conformationally constrained haptens. J Am Chem Soc. 2003;125(24):7164–5. doi:10.1021/ja034805t.

    Article  CAS  PubMed  Google Scholar 

  • Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, Everhart ET, Jones RT. Human pharmacology of the methamphetamine stereoisomers. Clin Pharmacol Ther. 2006;80(4):403–20. doi:10.1016/j.clpt.2006.06.013.

    Article  CAS  PubMed  Google Scholar 

  • Miller ML, Moreno AY, Aarde SM, Creehan KM, Vandewater SA, Vaillancourt BD, Wright Jr MJ, Janda KD, Taffe MA. A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biol Psychiatry. 2013;73(8):721–8. doi:10.1016/j.biopsych.2012.09.010.

    Article  CAS  PubMed  Google Scholar 

  • Moreno AY, Azar MR, Warren NA, Dickerson TJ, Koob GF, Janda KD. A critical evaluation of a nicotine vaccine within a self-administration behavioral model. Mol Pharm. 2010;7(2):431–41. doi:10.1021/mp900213u.

    Article  CAS  PubMed  Google Scholar 

  • Moreno AY, Mayorov AV, Janda KD. Impact of distinct chemical structures for the development of a methamphetamine vaccine. J Am Chem Soc. 2011;133(17):6587–95. doi:10.1021/ja108807j.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moreno AY, Azar MR, Koob GF, Janda KD. Probing the protective effects of a conformationally constrained nicotine vaccine. Vaccine. 2012;30(47):6665–70. doi:10.1016/j.vaccine.2012.08.064.

    Article  CAS  PubMed  Google Scholar 

  • Morishima HO, Whittington RA, Iso A, Cooper TB. The comparative toxicity of cocaine and its metabolites in conscious rats free. Anaesthesiology. 1999;90(6):1684–90. doi: 0000542-199906000-00025.

    Article  CAS  Google Scholar 

  • Müller K, Faeh C, Diederich F. Fluorine in pharmaceuticals: looking beyond intuition. Science. 2007;317(5846):1881–6. doi:10.1126/science.1131943.

    Article  PubMed  CAS  Google Scholar 

  • Nowak MA. Immune responses against multiple epitopes: a theory for immunodominance and antigenic variation. Semin Virol. 1996;7(1):83–92. doi:10.1006/smvy.1996.0010.

    Article  Google Scholar 

  • Oliver JL, Pashmi G, Barnett P, Mettens P, Biemans R, Monteyne P, Palmantier R, Gallagher T, Ramaya S, Wonnacott S. Development of an anti-cotinine vaccine to potentiate nicotine-based smoking cessation strategies. Vaccine. 2007;25(42):7354–62.

    Article  CAS  PubMed  Google Scholar 

  • Orson FM, Wang R, Brimijoin S, Kinsey BM, Singh RA, Ramakrishnan M, Wang HY, Kosten TR. The future potential for cocaine vaccines. Expert Opin Biol Ther. 2014;14(9):1271–83. doi:10.1517/14712598.2014.920319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osborne R, Thompson P, Joel S, Trew D, Patel N, Slevin M. The analgesic activity of morphine-6-glucuronide. Br J Clin Pharmacol. 1992;34(2):130–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pentel PR, Malin DH, Ennifar S, Hieda Y, Keyler DE, Lake JR, Milstein JR, Basham LE, Coy RT, Moon JWD, Naso R, Fattom A. A nicotine conjugate vaccine reduces nicotine distribution to brain and attenuates its behavioral and cardiovascular effects in rats. Pharmacol Biochem Behav. 2000;65(1):191–8.

    Article  CAS  PubMed  Google Scholar 

  • Perez-Reyes M, White WR, McDonald SA, Hill JM, Jeffcoat AR, Cook CE. Clinical effects of methamphetamine vapor inhalation. Life Sci. 1991;49(13):953–9. doi:10.1016/0024-3205(91)90078-P.

    Article  CAS  PubMed  Google Scholar 

  • Peri F. Clustered carbohydrates in synthetic vaccines. Chem Soc Rev. 2013;42(11):4543–56. doi:10.1039/c2cs35422e.

    Article  CAS  PubMed  Google Scholar 

  • Pöyhiä R, Seppälä T, Olkkola KT, Kalso E. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol. 1992;33(6):617–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pravetoni M, Keyler DE, Raleigh MD, Harris AC, LeSage MG, Mattson CK, Pettersson S, Pentel PR. Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats. Biochem Pharmacol. 2011;81(9):1164–70. doi:10.1016/j.bcp.2011.02.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pravetoni M, Keyler DE, Pidaparthi RR, Carroll FI, Runyon SP, Murtaugh MP, Earley CA, Pentel PR. Structurally distinct nicotine immunogens elicit antibodies with non-overlapping specificities. Biochem Pharmacol. 2012a;83(4):543–50.

    Article  CAS  PubMed  Google Scholar 

  • Pravetoni M, Le Naour M, Harmon TM, Tucker AM, Portoghese PS, Pentel PR. An oxycodone conjugate vaccine elicits drug-specific antibodies that reduce oxycodone distribution to brain and hot-plate analgesia. J Pharmacol Exp Ther. 2012b;341(1):225–32. doi:10.1124/jpet.111.189506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pravetoni M, Raleigh MD, Le Naour M, Tucker AM, Harmon TM, Jones JM, Birnbaum AK, Portoghese PS, Pentel PR. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats. Vaccine. 2012c;30(31):4617–24. doi:10.1016/j.vaccine.2012.04.101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pravetoni M, Le Naour M, Tucker AM, Harmon TM, Hawley TM, Portoghese PS, Pentel PR. Reduced antinociception of opioids in rats and mice by vaccination with immunogens containing oxycodone and hydrocodone haptens. J Med Chem. 2013;56(3):915–23. doi:10.1021/jm3013745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pravetoni M, Pentel PR, Potter DN, Chartoff EH, Tally L, LeSage MG. Effects of an oxycodone conjugate vaccine on oxycodone self-administration and oxycodone-induced brain gene expression in rats. PLoS One. 2014a;9(7), e101807. doi:10.1371/journal.pone.0101807.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pravetoni M, Vervacke JS, Distefano MD, Tucker AM, Laudenbach M, Pentel PR. Effect of currently approved carriers and adjuvants on the pre-clinical efficacy of a conjugate vaccine against oxycodone in mice and rats. PLoS One. 2014b;9(5), e96547. doi:10.1371/journal.pone.0096547.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pryde DC, Jones LH, Gervais DP, Stead DR, Blakemore DC, Selby MD, Brown AD, Coe JW, Badland M, Beal DM, Glen R, Wharton Y, Miller GJ, White P, Zhang N, Benoit M, Robertson K, Merson JR, Davis HL, McCluskie MJ. Selection of a novel anti-nicotine vaccine: influence of antigen design on antibody function in mice. PLoS One. 2013;8(10), e76557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raleigh MD, Pravetoni M, Harris AC, Birnbaum AK, Pentel PR. Selective effects of a morphine conjugate vaccine on heroin and metabolite distribution and heroin-induced behaviors in rats. J Pharmacol Exp Ther. 2013;344(2):397–406. doi:10.1124/jpet.112.201194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramakrishnan M, Kinsey BM, Singh RA, Kosten TR, Orson FM. Hapten optimization for cocaine vaccine with improved cocaine recognition. Chem Biol Drug Des. 2014;84(3):354–63. doi:10.1111/cbdd.12326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rook E, Huitema AR, van den Brink W, van Ree J, Beijnen J. Population pharmacokinetics of heroin and its major metabolites. Clin Pharmacokinet. 2006a;45(4):401–17. doi:10.2165/00003088-200645040-00005.

    Article  CAS  PubMed  Google Scholar 

  • Rook EJ, Van Ree JM, Van Den Brink W, Hillebrand MJX, Huitema ADR, Hendriks VM, Beijnen JH. Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients. Basic Clin Pharmacol. 2006b;98(1):86–96. doi:10.1111/j.1742-7843.2006.pto_233.x.

    Article  CAS  Google Scholar 

  • Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed. 2002;41(14):2596–9. doi:10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4.

    Article  CAS  Google Scholar 

  • Sakurai M, Wirsching P, Janda KD. Design and synthesis of a cocaine-diamide hapten for vaccine development. Tetrahedron Lett. 1996;37(31):5479–82. doi:10.1016/0040-4039(96)01170-7.

    Article  CAS  Google Scholar 

  • Schep LJ, Slaughter RJ, Beasley DMG. The clinical toxicology of metamfetamine. Clin Toxicol. 2010;48(7):675–94. doi:10.3109/15563650.2010.516752.

    Article  CAS  Google Scholar 

  • Schlosburg JE, Vendruscolo LF, Bremer PT, Lockner JW, Wade CL, Nunes AAK, Stowe GN, Edwards S, Janda KD, Koob GF. Dynamic vaccine blocks relapse to compulsive intake of heroin. Proc Natl Acad Sci U S A. 2013;110(22):9036–41. doi:10.1073/pnas.1219159110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schneerson R, Kubler-Kielb J, Liu T-Y, Dai Z-D, Leppla SH, Yergey A, Backlund P, Shiloach J, Majadly F, Robbins JB. Poly(γ-d-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of bacillus anthracis: a potential addition to the anthrax vaccine. Proc Natl Acad Sci. 2003;100(15):8945–50. doi:10.1073/pnas.1633512100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schramm W, Craig PA, Smith RH, Berger GE. Cocaine and benzoylecgonine in saliva, serum, and urine. Clin Chem. 1993;39(3):481–7.

    CAS  PubMed  Google Scholar 

  • Seleman M, Chapy H, Cisternino S, Courtin C, Smirnova M, Schlatter J, Chiadmi F, Scherrmann J-M, Noble F, Marie-Claire C. Impact of P-glycoprotein at the blood-brain barrier on the uptake of heroin and its main metabolites: behavioral effects and consequences on the transcriptional responses and reinforcing properties. Psychopharmacology (Berl). 2014;231(16):3139–49. doi:10.1007/s00213-014-3490-9.

    Article  CAS  Google Scholar 

  • Selley DE, Cao C-C, Sexton T, Schwegel JA, Martin TJ, Childers SR. μ Opioid receptor-mediated G-protein activation by heroin metabolites: evidence for greater efficacy of 6-monoacetylmorphine compared with morphine. Biochem Pharmacol. 2001;62(4):447–55. doi:10.1016/S0006-2952(01)00689-X.

    Article  CAS  PubMed  Google Scholar 

  • Shen XY, Kosten TA, Lopez AY, Kinsey BM, Kosten TR, Orson FM. A vaccine against methamphetamine attenuates its behavioral effects in mice. Drug Alcohol Depen. 2013;129(1-2):41–8. doi:10.1016/j.drugalcdep.2012.09.007.

    Article  CAS  Google Scholar 

  • Skibinski DAG, Baudner BC, Singh M, O’Hagan DT. Combination vaccines. J Global Infect Dis. 2011;3(1):63–72.

    Article  Google Scholar 

  • Skopp G, Ganssmann B, Cone EJ, Aderjan R. Plasma concentrations of heroin and morphine-related metabolites after intranasal and intramuscular administration. J Anal Toxicol. 1997;21(2):105–11. doi:10.1093/jat/21.2.105.

    Article  CAS  PubMed  Google Scholar 

  • Stowe GN, Schlosburg JE, Vendruscolo LF, Edwards S, Misra KK, Schulteis G, Zakhari JS, Koob GF, Janda KD. Developing a vaccine against multiple psychoactive targets: a case study of heroin. CNS Neurol Disord Drug Targets. 2011;10(8):865–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tars K, Kotelovica S, Lipowsky G, Bauer M, Beerli RR, Bachmann MF, Maurer P. Different binding modes of free and carrier-protein-coupled nicotine in a human monoclonal antibody. J Mol Biol. 2012;415(1):118–27. doi:10.1016/j.jmb.2011.10.042.

    Article  CAS  PubMed  Google Scholar 

  • Tietze LF, Arlt M, Beller M, Gl üsenkamp K-H, Jähde E, Rajewsky MF. Anticancer agents, 15. Squaric acid diethyl ester: a new coupling reagent for the formation of drug biopolymer conjugates. Synthesis of squaric acid ester amides and diamides. Chem Ber. 1991;124(5):1215–21. doi:10.1002/cber.19911240539.

    Article  CAS  Google Scholar 

  • Tornøe CW, Christensen C, Meldal M. Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem. 2002;67(9):3057–64. doi:10.1021/jo011148j.

    Article  PubMed  CAS  Google Scholar 

  • Ulrich S, Boturyn D, Marra A, Renaudet O, Dumy P. Oxime ligation: a chemoselective click-type reaction for accessing multifunctional biomolecular constructs. Chem Eur J. 2014;20(1):34–41. doi:10.1002/chem.201302426.

    Article  CAS  PubMed  Google Scholar 

  • Umans JG, Inturrisi CE. Pharmacodynamics of subcutaneously administered diacetylmorphine, 6-acetylmorphine and morphine in mice. J Pharmacol Exp Ther. 1981;218(2):409–15.

    CAS  PubMed  Google Scholar 

  • Wagena EJ, de Vos A, Horwith G, van Schayck CP. The immunogenicity and safety of a nicotine vaccine in smokers and nonsmokers: results of a randomized, placebo-controlled phase 1/2 trial. Nicotine Tob Res. 2008;10(1):213–8. doi:10.1080/14622200701704921.

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Guo Z. Synthetic and immunological studies of sTn derivatives carrying substituted phenylacetylsialic acids as cancer vaccine candidate. ACS Med Chem Lett. 2011;2(5):373–8. doi:10.1021/ml100313d.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang F, Zheng X-J, Huo C-X, Wang Y, Zhang Y, Ye X-S. Enhancement of the immunogenicity of synthetic carbohydrate vaccines by chemical modifications of STn antigen. ACS Chem Biol. 2010;6(3):252–9. doi:10.1021/cb100287q.

    Article  CAS  Google Scholar 

  • Yuki D, Kikuchi A, Miura N, Kakehi A, Onozawa M. Good relationship between saliva cotinine kinetics and plasma cotinine kinetics after smoking one cigarette. Regul Toxicol Pharm. 2013;67(2):240–5. doi:10.1016/j.yrtph.2013.08.002.

    Article  CAS  Google Scholar 

  • Zheng F, Zhan C-G. Structure-and-mechanism-based design and discovery of therapeutics for cocaine overdose and addiction. Org Biomol Chem. 2008;6(5):836–43. doi:10.1039/B716268E.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Karen C. Collins & Kim D. Janda

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  1. Karen C. Collins
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  2. Kim D. Janda
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  1. National Institute on Drug Abuse, National Institutes of Health, Bethesda, USA

    Ivan D. Montoya

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Collins, K.C., Janda, K.D. (2016). Hapten Design for Anti-addiction Vaccine Development. In: Montoya, I. (eds) Biologics to Treat Substance Use Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-23150-1_18

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