El estado actual de las vacunas contra las drogas
Contenido principal del artículo
Resumen
Introducción: por lo común, la adicción a las drogas se trata con psicoterapia y farmacología que evita la unión de las sustancias psicoactivas a receptores específicos en el cerebro. El resultado de estos tratamientos no ha sido del todo satisfactorio, por lo que el desarrollo de terapias más eficaces representa un reto constante para tratar las adicciones. Una alternativa a la farmacología antiadictiva es la vacunación activa dirigida contra las sustancias de abuso.
Objetivo: esta revisión reúne la información disponible sobre los fundamentos y avances científicos en la generación de una terapia inmunológica, que coadyuve al tratamiento de la adicción a sustancias como la heroína-morfina, la cocaína, la nicotina y la anfetamina.
Método: se consideraron los reportes científicos disponibles en PubMed –de 2005 a abril de 2017–, sobre los fundamentos, la metodología empleada, los estudios preclínicos y clínicos, y los resultados obtenidos en dichas investigaciones para generar vacunas contra las drogas.
Resultados: las vacunas lograron mitigar los efectos producidos por las sustancias en los estudios preclínicos en modelos de estudio en animales; sin embargo, con pacientes humanos los resultados no han sido del todo satisfactorios.
Discusión y conclusiones: a pesar de los esfuerzos realizados por diferentes grupos de investigación y compañías farmacéuticas para generar vacunas terapéuticas contra el uso de diferentes drogas, ninguna ha alcanzado la fase III de estudios clínicos. En la actualidad, se continúa con los esfuerzos para lograr que las vacunas contra las adicciones alcancen su máxima eficiencia y eficacia, y contribuyan al tratamiento de la adicción a las drogas.
Detalles del artículo
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Akbarzadeh, A., Mehraby, M., Zarbakhsh, M., & Farzaneh, H. (1999). Design and synthesis of a morphine-6-succinyl-bovine serum albumin hapten for vaccine development. Biotechnology Applied Biochemistry, 30(2), 139-146. doi: 10.1111/j.1470-8744.1999.tb00904.x
Akbarzadeh, A., Norouzian, D., Farhangi, A., Mehrabi, M., Chiani, M., Zare, D., … Nikdel, A. (2009). Immunotherapy of 347 volunteer outpatient morphine addicts by human therapeutic morphine vaccine in Kermanshah Province of Iran. Journal Pharmacology and Toxicology, 4(1), 30-35. doi: 10.3923/jpt.2009.30.35
Anton, B., & Leff, P. (2006). A novel bivalent morphine/heroin vaccine that prevents relapse to heroin addiction in rodents. Vaccine 24(16), 3232-3240. doi: 10.1016/j.vaccine.2006.01.047
Barnett, V., Twycross, R., Mihalyo, M., & Wilcock, A. (2014). Opioid antagonists. Journal of Pain and Symptom Managemen, 47(2), 341-352. doi: 10.1016/j.jpainsymman.2013.12.223
Bremer, P. T., Schlosburg, J. E., Lively, J. M., & Janda, K. D. (2014). Injection route and TLR9 agonist addition significantly impact heroin vaccine efficacy. Molecular Pharmaceutics, 11(3), 1075-1080. doi: 10.1021/mp400631w
Brimijoin, S., Shen, X., Orson, F., & Kosten, T. (2013). Prospects, promise and problems on the road to effective vaccines and related therapies for substance abuse. Expert Review of Vaccines, 12(3), 323-332. doi: 10.1586/erv.13.1
Chou, R., Cruciani, R. A., Fiellin, D. A., Compton, P., Farrar, J. T., Haigney, M. C., … Zeltzer, L. (2014). Methadone safety: a clinical practice guideline from the American Pain Society and college on problems of drug dependence, in collaboration with the Heart Rhythm Society. The Journal of Pain, 15(4), 321-337. doi: 10.1016/j.jpain.2014.01.494
Cornuz, J., Zwahlen, S., Jungi, W. F., Osterwalder, J., Klingler, K., van Melle, G., … Cerny, T. (2008). A vaccine against nicotine for smoking cessation: a randomized controlled trial. PLoS ONE, 3(6), e2547. doi: 10.1371/journal.pone.0002547
Davids, E., & Gastpar, M. (2004). Buprenorphine in the treatment of opioid dependence. European Neuropsychopharmacology, 14(3), 209-216. doi: 10.1016/S0924-977X(03)00146-9
Desai, R. I., & Bergman, J. (2015). Effects of the nanoparticle-based vaccine, SEL-068, on nicotine discrimination in squirrel monkeys. Neuropsychopharmacology, 40(9), 2207-2216. doi: 10.1038/npp.2015.64
Desai, R. I., & Bergman, J. (2016). Nicotine-targeting nano-vaccines for smoking cessation. Neuropsychopharmacology, 41(1), 377-378. doi: 10.1038/npp.2015.234
Duryee, M. J., Bevins, R. A., Reichel, C. M., Murray, J. E., Dong, Y., Thiele, G. M., … Sanderson, S. D. (2009). Immune responses to methamphetamine by active immunization with peptide-based, molecular adjuvant-containing vaccines. Vaccine, 27(22), 2981-2988. doi: 10.1016/j.vaccine.2009.02.105
Esterlis, I., Hannestad, J. O., Perkins, E., Bois, F., D’Souza, D. C., Tyndale, R. F., … O’Malley, S. S. (2013). Effect of a nicotine vaccine on nicotine binding to b2*-nicotinic acetylcholine receptors in vivo in human tobacco smokers. American Journal of Psychiatry, 170(4), 399-407. doi: 10.1176/appi.ajp.2012.12060793
Fahim, R. E., Kessler, P. D., & Kalnik, M. W. (2013). Therapeutic vaccines against tobacco addiction. Expert Review of Vaccines, 12(3), 333-342. doi: 10.1586/erv.13.13
Farhangi, A., Akbarzadeh, A., Mehrabi, M. R., Chiani, M., Saffari, Z., Mortazavi, M., … Ghassemi, S. (2012). Immunotherapy of 436 morphine addicts by therapeutic morphine vaccine in Kerman Province (I.R. Iran). Journal of Vaccines and Vaccinology, 3(6), 1-6. doi: 10.4172/2157-7560.1000154
Fraser, C. C., Altreuter, D. H., Ilyinskii, P., Pittet, L., LaMothe, R. A., Keegan, M., … Kishimoto, T. K. (2014). Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates. Vaccine, 32(24), 2896-2903. doi: 10.1016/j.vaccine.2014.02.024
Haney, M, Gunderson, E. W., Jiang, H, Collins, E. D., & Foltin, R. W. (2010). Cocaine-specific anti-bodies blunt the subjective effects of smoked cocaine in humans. Biological Psychiatry, 67(1), 59- 65. doi: /10.1016/j.biopsych.2009.08.031
Hatsukami, D. K., Jorenby, D. E., González, D., Rigotti, N. A., Glover, E. D., Oncken, C. A, … Rennard, S. I. (2011). Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic. Clinical Pharmacology & Therapeutics, 89(3), 392-399. doi: 10.1038/clpt.2010.317
Hatsukami, D. K., Rennard, S., Jorenby, D., Fiore, M., Koopmeiners, J., de Vos, A., … Kalnik, M. W. (2005). Safety and immunogenicity of a nicotine conjugate vaccine in current smokers. Clinical Pharmacology & Therapeutics, 78(5), 456-467. doi: 10.1016/jclpt.2005.007
Hatsukami, D. K., Stead, L. F., & Gupta, P. C. (2008). Tobacco addiction. Lancet, 371(9629), 2027-2038. doi: 10.1016/s0140-6736(08)60871-5
Havermans, A., Vuurman, E. F., van den Hurk, J., Hoogsteder, P., & van Schayck, O. C. P. (2014). Treatment with a nicotine vaccine does not lead to changes in brain activity during smoking cue exposure or a working memory task. Addiction, 109(8), 1260-1267. doi: 10.1111/add.12577
Hicks, M. J., De, B. P., Rosenberg, J. B., Davidson, J. T., Moreno, A. Y., Janda K. D., … Crystal, R. G. (2011). Cocaine analog coupled to disrupted adenovirus: a vaccine strategy to evoke high-titer immunity against addictive drugs. Molecular Therapy, 19(3), 612-619. doi: 10.1038/mt.2010.280
Hoogsteder, P. H. J., Kotz, D., van Spiegel, P. I., Viechtbauer, W., & van Schayck, O. C. (2014). Efficacyof the nicotine vaccine 3’-AmNic-rEPA (NicVAX) co-administered with varenicline and counselling for smoking cessation: a randomized placebo-controlled trial. Addiction, 109(8), 1252-1259. doi: 10.1111/add.12573
Kinsey, B. (2014). Vaccines against drugs of abuse: where are we now? Therapeutic Advances in Vaccines, 2(4), 106-117. doi: 10.1177/2051013614537818
Kinsey, B. M., Jackson, D. C., & Orson, F. M. (2009). Anti-drug vaccines to treat substance abuse. Immunology and Cell Biology, 87(4), 309-314. doi: 10.1038/icb.2009.17
Kosten, T. A., Shen, X. Y., O’Malley, P. W., Kinsey, B. M., Lykissa, E. D., Orson, F. M., … Kosten, T. R. (2013). A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 45, 223-229. doi: 10.1016/j.pnpbp.2013.05.012
Kosten, T. R., Domingo, C. B., Shorter, D., Orson, F., Green, C., Somoza, E., … Kampman, K. (2014). Vaccine for cocaine dependence: a randomized double-blind placebo-controlled efficacy trial. Drug and Alcohol Dependence, 140, 42-47. doi: 10.1016/j.drugalcdep.2014.04.003
Kosten, T., & Owens, S. M. (2005). Immunotherapy for the treatment of drug abuse. Pharmacology & Therapeutics, 108(1), 76-85. doi: 10.1016/j.pharmthera.2005.06.009
Li, Q. Q., Luo, Y. X., Sun, C. Y., Xue, Y. X., Zhu, W. L., Shi, H. S., … Lu, L. (2011). A morphine/heroin vaccine with new hapten design attenuates behavioral effects in rats. Journal of Neurochemistry, 119(6), 1271-1281. doi: 10.1111/j.1471-4159.2011.07502.x
Li, Q. Q., Sun, C. Y., Luo, Y. X., Xue, Y. X., Meng, S. Q., Xu, L. Z., … Sun, H. Q. (2015). A conjugate vaccine attenuates morphine-and heroin-induced behavior in rats. The International Journal of Neuropsychopharmacology, 18(5), 1-11. doi: 10.1093/ ijnp/pyu093
Maoz, A., Hicks, M. J., Vallabhjosula, S., Synan, M., Kothari, P. J., Dyke, J. P., … Crystal, R. G. (2013). Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter. Neuropsychopharmacology, 38(11), 2170-2178. doi: 10.1038/npp.2013.114
Martell, B. A., Mitchell, E., Poling, J., Gonsai, K., & Kosten, T. R. (2005). Vaccine pharmacotherapy for the treatment of cocaine dependence. Biological Psychiatry, 58(2), 158-164. doi: 10.1016/j. biopsych.2005.04.032
Martell, B. A., Orson, F. M., Poling, J., Mitchell, E., Rossen, R. D., Gardner, T., ... Kosten, T. R. (2009). Cocaine vaccine for the treatment of cocaine dependence in methadone-maintained patients: a randomized, double-blind, placebo-controlled efficacy trial. Archives of General Psychiatry, 66(10), 1116-1123. doi: 10.1001/archgenpsychiatry.2009.128
Maurer, P., Jennings, G. T., Willers, J., Rohner, F., Lindman, Y., Roubicek, K., … Bachmann, M. F. (2005). A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity. European Journal of Immunology, 35(7), 2031-2040. doi: 10.1002/eji.200526285
Miller, M. L., Aarde, S. M., Moreno, A. Y., Creehan, K. M., Janda, K. D., & Taffe, M. A. (2015). Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats. Drug Alcohol Dependence, 153, 29-36. doi: 10.1016/j.drugalcdep.2015.06.014
Miller, M. L., Moreno, A. Y., Aarde, M., Creehan, K. M., Vandewater, S. A., Vaillancourt, B. D., … Taffe, M. A. (2013). A methamphetamine vaccine attenuates methamphetamine-induced disruptions in thermoregulation and activity in rats. Biological Psychiatry, 73(8), 721-728. doi: 10.1016/j.biopsych.2012.09.010
Moher, D., Liberati, A., Tetzlaff, J., & Altman D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ, 339, b2535. doi: 10.1136/bmj.b2535
Montoya, I. D. (2012). Advances in the development of biologics to treat drug addictions and overdose. Adicciones, 24(2), 95-103. doi: 10.20882/adicciones.101
Montoya, I. D. (Ed.). (2016). Biologics to treat substance use disorders. Switzerland: Springer International Publishing. doi: 10.1007/978-3-319-23150-1
Moreno, A. Y., & Janda, K. D. (2009). Immunopharmacotherapy: vaccination strategies as a treatment for drug abuse and dependence. Pharmacology Biochemistry and Behavior, 92(2), 199-205. doi: 10.1016/j.pbb.2009.01.015
Moreno, A. Y., Mayorov, A. V., & Janda, K. D. (2011). Impact of distinct chemical structures for the development of a methamphetamine vaccine. Journal of American Chemical Society, 133(17), 6587-6595. doi: 10.1021/ja108807j
Ohia-Nwoko, O., Kosten, T. A., & Haile, C. N. (2016). Animal models and the development of vaccines to treat substance use disorders international review of neurobiology. International Review of Neurobiology, 126, 263-291. doi: 10.1016/bs.irn.2016.02.009
Orson, F. M., Rossen, R. D., Shen, X., López, A. Y., Wu, Y., & Kosten, T. R. (2013). Spontaneous development of IGM anti-cocaine antibodies in habitual cocaine users: effect on IGG antibody responses to a cocaine cholera toxin b conjugate vaccine. The American Journal on Addictions, 22(2), 169-174. doi: 10.1111/j.1521-0391.2013.00314.x
Orson, F. M., Wang, R., Brimijoin, S., Kinsey, B. M., Singh, R. A. K., Ramakrishnan, M., … Kosten, T. R. (2014). The future potential for cocaine vaccines. Expert Opinion on Biological Therapy, 14(9), 1271-1283. doi: 10.1517/14712598.2014.920319
Raleigh, M. D., Pentel, P. R., & LeSage, M. G. (2014). Pharmacokinetic correlates of the effects of a heroin vaccine on heroin self-administration in rats. PLoS One, 9(12), e115696. doi: 10.1371/journal.pone.0115696
Rüedi-Bettschen, D., Wood, S. L., Gunnell, M. G., West, C. M., Pidaparthi, R. R., Carroll F. I., … Owens, S. M. (2013). Vaccination protects rats from methamphetamine-induced impairment of behavioral responding for food. Vaccine, 31(141), 4596-4602. doi: 10.1016/j.vaccine.2013.07.038
Salazar-Juárez, A., Barbosa-Méndez, S., Jurado, N., Hernández-Miramontes, R., Leff, P., & Antón, B. (2016). Mirtazapine prevents induction and expression of cocaine-induced behavioral sensitization in rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 68, 15-24. doi: 10.1016/j.pnpbp.2016.02.010
Schlosburg, J. E., Vendruscolo, L. F., Bremer, P. T., Lockner, J. W., Wade, C. L., Nunes, A. A. K.,… Koob, G. F. (2013). Dynamic vaccine blocks relapse to compulsive intake of heroin. Proceedings of the National Academy of Sciences of the United States of America, 110(22), 9036-9041. doi: 10.1073/pnas.1219159110
Shen, X. Y., Kosten, T. A., López, A. Y., Kinsey, B. M., Kosten, T. R., & Orson, F. M. (2013). A vaccine against methamphetamine attenuates its behavioral effects in mice. Drug Alcohol Dependence, 129(1-2), 41-48. doi: 10.1016/j.drugalcdep.2012.09.007
Shen, X., Orson, F. M., & Kosten, T. R. (2011). Anti-addiction vaccines. F1000 Medicine Reports, 3, 20. doi: 10.3410/M3-20
Shorter, D., & Kosten, T. R. (2011). Novel pharmacotherapeutic treatments for cocaine addiction. BMC Medicine, 9(119). doi: 10.1186/1741-7015-9-119
Stowe, G. N., Schlosburg, J. E., Vendruscolo, L. F., Edwards, S., Misra, K. K., Schulteis, G., … Janda K. D. (2011). Developing a vaccine against multiple psychoactive targets: a case study of heroin. Central Nervous System & Neurological Disorders Drug Targets, 10(8), 865-875. doi: 10.2174/187152711799219316
Stowe, G. N., Vendruscolo, L. F., Edwards, S., Schlosburg, J. E., Misra, K. K., Schulteis, G., … Janda, K. D. (2011). A vaccine strategy that induces protective immunity against heroin. Journal of Medicinal Chemistry, 54(14), 5195-5204. doi: 10.1021/jm200461m
Tonstad, S., Heggen, E., Giljam, H., Lagerbäck, P. Å., Tønnesen, P., Wikingsson, L.D., … Fagerström, K. O. (2013). Niccine®, a nicotine vaccine, for relapse prevention: a phase II, randomized, placebo-controlled, multicenter clinical trial. Nicotine & Tobacco Research, 15(9), 1492-1501. doi: 10.1093/ntr/ntt003
Torres, O. B., Jalah, R., Rice, K. C., Li, F., Antoline, J.F., Iyer, M. R., ... Matyas, G. R. (2014). Characterization and optimization of heroin hapten-BSA conjugates: method development for the synthesis of reproducible hapten-based vaccines. Analytical and Bioanalytical Chemistry, 406(24), 5927-5937. doi: 10.1007/s00216-014-8035-x
Veilleux, J. C., Colvin, P. J., Anderson, J., York, C., & Heinz, A. J. (2010). A review of opioid dependence treatment: pharmacological and psychosocial interventions to treat opioid addiction. Clinical Psychology Review, 30(2), 155-166. doi: 10.1016/j.cpr. 2009.10.006
Wagena, E. J., de Vos, A., Horwith, G., & van Schayck, C. P. (2008). The immunogenicity and safety of a nicotine vaccine in smokers and nonsmokers: results of a randomized, placebo-controlled phase 1/2 trial. Nicotine & Tobacco Research, 10(1), 213-218. doi: 10.1080/14622200701704921
Wee, S., Hicks, M. J., De, B. P., Rosenberg, J. B., Moreno, A. Y., Kaminsky, S. M., … Koob, G. F. (2012). Novel cocaine vaccine linked to a disrupted adenovirus gene transfer vector blocks cocaine psychostimulant and reinforcing effects. Neuropsychopharmacology, 37(5), 1083-1091. doi: 10.1038/npp.2011.200
Zalewska-Kaszubska, J. (2015). Is immunotherapy an opportunity for effective treatment of drug addiction? Vaccine, 33(48), 6545-6551. doi: 10.1016/j.vaccine.2015.09.079