Development of a Practical Heroin-HIV Vaccine

实用海洛因艾滋病毒疫苗的开发

• 批准号: 8515985
• 负责人: Gary R. Matyas
• 金额: $ 139.27万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8515985
• 关键词: Adjuvant; Affinity; Agreement; Anesthetics; Antibodies; Collaborations; Development; Drug Formulations; Epitopes; Goals; HIV; HIV Envelope Protein gp120; HIV Envelope Protein gp41; HIV vaccine; HIV-1; Haptens; Heroin; Heroin Abuse; Immune; Immune response; In Vitro; Infection; Lead; Military Personnel; National Institute of Drug Abuse; Overdose; Peptide Vaccines; Peptides; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Physiological; Preclinical Testing; Prevention; Relative (related person); Research; Rodent; Specificity; Vaccines; base; immunogenicity; nonhuman primate; pre-clinical; programs

DESCRIPTION (provided by applicant): In recognition of the frequent association of HIV-1 infection with the use of injected heroin, the US Military HIV Research Program (MHRP) and the National Institute for Drug Abuse initiated a collaborative interagency agreement in 2010 to examine the feasibility of creating a practical combination anti-heroin vaccine (AHV) and HIV vaccine product. Based on the recent multi- institutional immune correlate analyses of the successful MHRP RV144 Thai trial that demonstrated that antibodies directed to the HIV-1 gp120 V2 loop correlated with protection against HIV-1 infection, together with previous studies that demonstrated the feasibility of immunoprotection to heroin abuse, MHRP believes that a unique opportunity exists to create a candidate peptide vaccine both to HIV-1 and heroin. As a result of this collaboration, a safe, inexpensive, heroin-hapten-peptide-based, easily manufactured, strongly adjuvanted combination candidate AHV/HIV vaccine product has now been created that is ready for optimization and advanced preclinical testing for anticipated phase I and phase II clinical trials. If successful it is anticipated that this vaccine will provid a deployable heroin vaccine and will represent a major advance for creation of a practical and effective HIV vaccine. The major goals are to: (1) optimize the hapten-gp41/gp120-T helper peptide-adjuvant-carrier formulation by examining the relative immune responses in rodents with three alternative identified lead heroin haptens; (2) perform advanced preclinical immunogenicity studies in rodents with the final lead formulation to examine antibody isotypes, affinities, specificities for heroin and HIV gp41 and gp120-V2 loop epitopes; (3) examine vaccine-induced anti-heroin antibodies for prevention of anesthetic effects and prevention of physiological effects associated with drug overdose in rodents and non-human primates; (4) perform neutralization and other in vitro functional analyses of vaccine- i

描述（由申请人提供）：认识到HIV-1感染与注射海洛因使用的频繁关联，美国军事HIV研究计划（MHRP）和国家药物滥用研究所于2010年启动了一项机构间合作协议，以审查创建抗海洛因疫苗（AHV）和HIV疫苗产品的实用组合的可行性。基于最近对成功的MHRP RV144泰国试验的多机构免疫相关分析，该试验表明，针对HIV-1 gp120 V2环的抗体与防止HIV-1感染相关，以及先前证明免疫保护海洛因滥用的可行性的研究，MHRP认为存在一个独特的机会来创造一种既针对HIV-1又针对海洛因的候选肽疫苗。此次合作的结果是，一种安全、廉价、以海洛因半肽为基础、易于制造、强佐剂组合的AHV/HIV候选疫苗产品现已问世，该产品已准备好进行优化和高级临床前测试，用于预期的I期和II期临床试验。如果成功，预计这种疫苗将提供一种可部署的海洛因疫苗，并将是研制实用和有效的艾滋病毒疫苗方面的重大进展。主要目标是：(1)通过检测三种鉴定的铅海洛因半抗原在啮齿动物中的相对免疫反应，优化半抗原-gp41/gp120-T辅助肽-佐剂载体配方；(2)在啮齿类动物中进行临床前免疫原性研究，用最终的先导制剂检测海洛因和HIV的gp41和gp120-V2环表位的抗体同型、亲和力和特异性；(3)检测疫苗诱导的抗海洛因抗体在啮齿类动物和非人灵长类动物中预防麻醉效应和预防药物过量相关的生理效应；(4)对I型疫苗进行中和和其他体外功能分析