Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
基本信息
- 批准号:8076921
- 负责人:
- 金额:$ 34.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-07-15 至 2013-05-31
- 项目状态:已结题
- 来源:
- 关键词:6-O-monoacetylmorphineAODD relapseAbsence of pain sensationAdjuvantAffinityAluminum HydroxideAmericanAnimal ModelAnimalsAntibodiesAntibody AffinityAntibody FormationAustraliaBehaviorBehavioralBindingBiological ModelsBlood - brain barrier anatomyBlood CirculationBlood-Borne PathogensBrainCarrier ProteinsCharacteristicsChemicalsChinaCholera ToxinChronicClinicalClinical ResearchCocaineCodeineCollaborationsConjugate VaccinesCountryDataDependenceDeveloped CountriesDeveloping CountriesDevelopmentDoseDrug CarriersDrug KineticsDrug PrescriptionsDrug abuseDrug usageEconomicsEffectivenessEmulsionsFutureHIVHaptensHealthHeroinHeroin AbuseHourHumanImmune SeraImmune responseImmunizationImmunoglobulin GImmunologic MemoryIndiaIndividualInjection of therapeutic agentLifeLinkLiverMeasuresMembrane ProteinsMethamphetamineMethodsModelingMonitorMorphineMorphine DependenceMorphine Derivatives Including CocaineMotor ActivityMusNarcoticsNeisseria meningitidisNeuraxisNeurotransmittersNicotineOilsOligonucleotidesOpiate AddictionOpiatesOralPenetrationPharmaceutical PreparationsPharmacodynamicsPhysiologicalPositioning AttributePrevention approachProdrugsProteinsPublishingRattusRelapseResearchResearch PersonnelRodent ModelRoleRouteRussiaScreening procedureSelf AdministrationSeriesSiteSpeedSupplementationT cell responseTarget PopulationsTestingTherapeuticTiterMaxUniversitiesVaccinatedVaccinationVaccine AdjuvantVaccine DesignVaccinesWaterWorkaddictionattenuationcandidate selectioncross reactivitydesigndisorder later incidence preventiondrug cravingdrug reinforcementeffective therapyesterasehydroxyl groupinterestintravenous injectionmethadone clinic/centermonophosphoryl lipid Amorphine-6-glucuronidemouse modelnormorphinenovelopioid abusephase 2 studypreclinical studyprogramsprotein complexresponsesmall moleculesocialsuccesstheoriestherapeutic vaccinetooltreatment programvaccine candidatevaccine developmentvaccine evaluation
项目摘要
DESCRIPTION (provided by applicant): Opiate abuse/dependence has profound social and economic effects in all parts of the world. Intravenous injection is the major route of illicit opiate drug administration in most countries, although abuse of oral prescription drugs has been recently increasing. While methadone clinics and other treatment programs can be effective, the expense of the support programs and medications can inhibit broad application of these methods to the target population, especially in less developed nations, and can be quite controversial in others. Without more effective treatment or prevention approaches for drug abuse, addiction to narcotics is very likely to accelerate further. An especially attractive alternative approach against opiate addiction in this context is immunization, a potentially powerful tool in assisting individuals to stop their abuse of these substances. Although there are many forms of opiate abuse, it is essential to focus experimental efforts for vaccine development on a limited number of specific agents to establish the effectiveness of this approach. Any effective vaccine for heroin will have to elicit high levels of antibodies that bind heroin, morphine, and other active metabolites, since concentrations of pharmacologically active opiates exceed the usual amounts of specific antibody. As our preliminary data shows, the outer membrane protein complex (OMPC) of Neisseria meningitidis is particularly attractive as a carrier for the morphine conjugate vaccine, since it elicits early, high level responses to the drug. The antibody response and the inhibition of morphine pharmacological effects can be directly evaluated in rodent model systems, permitting the rapid development of candidate vaccines. This proposal focuses on therapeutic heroin/morphine vaccines with these hypotheses: 1) Screening morphine linked to different carrier proteins or to a lipopeptide construct will allow selection of a vaccine that, along with appropriate adjuvant(s), can rapidly elicit a sufficient quantity and quality of specific antibody to block the pharmacological activity of heroin and its active metabolites. 2) The quality and quantity of the antibodies induced by these vaccines that can block opiate associated analgesia will also block heroin induced locomotor activity and reinstatement of heroin self administration in the rat model. Morphine will be conjugated to two highly effective protein carriers: OMPC and cholera toxin b (CTB). These conjugate vaccines will be compared with a novel self-adjuvanting lipopeptide vaccine prepared by D. C. Jackson (University of Melbourne, Australia). A panel of adjuvants compatible with human use will be examined to maximize the antibody quantity, quality (affinity), and persistence as well as the inhibition of opiate induced analgesia, locomotor activity, and reinstatement of drug self-administration. Successful completion of this project will continue the collaboration between American and Australian investigators that will be ideally positioned to get a vaccine quickly into clinical development studies.
PUBLIC HEALTH RELEVANCE: Opiate abuse/dependence has had profound social and economic effects in all parts of the world. Intravenous injection is the dominant route of illicit opiate drug use, magnifying the health consequences of addiction through the spread of various blood borne pathogens. An especially attractive alternative approach to help treat opiate addiction is vaccination against these drugs, which could become a powerful tool in assisting individuals to stop their abuse of these substances. This research will develop such vaccines by attaching morphine to carrier molecules and testing immunization conditions that will stimulate high levels of antibody to block the effects of heroin and morphine on relapse to drug self administration in the mouse model of opiate abuse.
说明(申请人提供):鸦片滥用/依赖在世界各地具有深远的社会和经济影响。静脉注射是大多数国家非法阿片类药物给药的主要途径,尽管近年来口服处方药的滥用有所增加。虽然美沙酮诊所和其他治疗计划可能是有效的,但支持计划和药物的费用可能会阻碍这些方法在目标人群中的广泛应用,特别是在欠发达国家,在其他国家可能会相当有争议。如果没有更有效的药物滥用治疗或预防方法,对毒品的上瘾很可能会进一步加速。在这方面,防止鸦片成瘾的一种特别有吸引力的替代办法是免疫接种,这是协助个人停止滥用这些物质的一种潜在的有力工具。尽管有多种形式的阿片类药物滥用,但至关重要的是,必须将疫苗开发的实验努力集中在有限数量的特定制剂上,以确定这种方法的有效性。任何有效的海洛因疫苗都必须诱导高水平的抗体来结合海洛因、吗啡和其他活性代谢物,因为药理活性阿片类药物的浓度超过了通常的特异性抗体。我们的初步数据显示,脑膜炎奈瑟氏菌的外膜蛋白复合体(OMPC)作为吗啡结合疫苗的载体特别有吸引力,因为它能引起早期、高水平的药物反应。在啮齿动物模型系统中可以直接评估抗体反应和对吗啡药理作用的抑制,从而使候选疫苗的快速开发成为可能。1)筛选与不同载体蛋白或脂肽结构相连的吗啡,将允许选择一种疫苗,该疫苗与适当的佐剂(S)一起,可以迅速产生足够数量和质量的特异性抗体来阻断海洛因及其活性代谢物的药理活性。2)这些疫苗诱导的抗体的质量和数量都能阻断阿片类药物相关的镇痛作用,也将阻断海洛因诱导的自主活动和海洛因自我给药的恢复。吗啡将连接到两个高效的蛋白质载体:OMPC和霍乱毒素b(CTB)。这些结合疫苗将与澳大利亚墨尔本大学的D.C.Jackson研制的一种新型自我调节脂肽疫苗进行比较。将检查一组与人类使用相容的佐剂,以最大限度地提高抗体的数量、质量(亲和力)和持久性,以及抑制阿片类药物诱导的止痛、运动活性和恢复药物的自我给药。该项目的成功完成将继续美国和澳大利亚研究人员之间的合作,这将是将疫苗迅速投入临床开发研究的理想地位。
与公共卫生有关:鸦片滥用/依赖在世界各地产生了深远的社会和经济影响。静脉注射是非法使用鸦片类药物的主要途径,通过传播各种血液传播的病原体放大了成瘾对健康的影响。帮助治疗阿片成瘾的一个特别有吸引力的替代方法是针对这些药物接种疫苗,这可能成为帮助个人停止滥用这些物质的有力工具。这项研究将通过将吗啡附着在载体分子上并测试免疫条件来开发这样的疫苗,该免疫条件将刺激高水平的抗体,以阻断海洛因和吗啡在阿片类药物滥用小鼠模型中复发到自我给药的影响。
项目成果
期刊论文数量(0)
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FRANK M ORSON其他文献
FRANK M ORSON的其他文献
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{{ truncateString('FRANK M ORSON', 18)}}的其他基金
Development of Novel Vaccines for Cocaine Abuse
针对可卡因滥用的新型疫苗的开发
- 批准号:
8316422 - 财政年份:2010
- 资助金额:
$ 34.93万 - 项目类别:
Development of Novel Vaccines for Cocaine Abuse
针对可卡因滥用的新型疫苗的开发
- 批准号:
8707412 - 财政年份:2010
- 资助金额:
$ 34.93万 - 项目类别:
Development of Novel Vaccines for Cocaine Abuse
针对可卡因滥用的新型疫苗的开发
- 批准号:
8535713 - 财政年份:2010
- 资助金额:
$ 34.93万 - 项目类别:
Development of Novel Vaccines for Cocaine Abuse
针对可卡因滥用的新型疫苗的开发
- 批准号:
8147727 - 财政年份:2010
- 资助金额:
$ 34.93万 - 项目类别:
Developing Immunotherapeutics for Methamphetamine Abuse
开发针对甲基苯丙胺滥用的免疫疗法
- 批准号:
7894904 - 财政年份:2009
- 资助金额:
$ 34.93万 - 项目类别:
Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
- 批准号:
7695925 - 财政年份:2009
- 资助金额:
$ 34.93万 - 项目类别:
Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
- 批准号:
7892450 - 财政年份:2009
- 资助金额:
$ 34.93万 - 项目类别:
Vaccines for Sustainable Therapy of Opiate Addiction
用于阿片成瘾可持续治疗的疫苗
- 批准号:
8277437 - 财政年份:2009
- 资助金额:
$ 34.93万 - 项目类别: