Development of a Practical Heroin-HIV Vaccine

描述(由申请人提供)：认识到艾滋病毒-1感染经常与注射海洛因的使用有关，美国军方艾滋病毒研究计划(MHRP)和国家药物滥用研究所在2010年发起了一项合作机构间协议，以审查创建实用的抗海洛因疫苗(AHV)和艾滋病毒疫苗产品的可行性。根据最近对成功的MHRP RV144泰国试验的多机构免疫相关性分析，证明针对HIV-1 gp120 V2环的抗体与预防HIV-1感染相关，以及先前证明对海洛因滥用进行免疫保护的可行性的研究，MHRP认为存在创造针对HIV-1和海洛因的候选多肽疫苗的独特机会。由于这一合作，一种安全、廉价、以海洛因半抗原肽为基础、易于制造、强佐剂的候选AHV/HIV联合疫苗产品现已问世，该产品已准备好用于预期的第一阶段和第二阶段临床试验的优化和高级临床前测试。如果成功，预计这种疫苗将提供一种可部署的海洛因疫苗，并将在创造实用和有效的艾滋病毒疫苗方面取得重大进展。主要目标是：(1)通过检测三种可供选择的铅海洛因半抗原在啮齿类动物中的相对免疫反应，优化半抗原-gp41/gp120-T辅助多肽载体制剂；(2)用最终的铅配方在啮齿动物中进行高级临床前免疫原性研究，以检测海洛因和HIV gp41和gp120-V2环表位的抗体亚型、亲和力和特异性；(3)检测疫苗诱导的抗海洛因抗体，以防止在啮齿动物和非人类灵长类动物中与药物过量相关的麻醉效应和生理效应；(4)进行疫苗I的中和和其他体外功能分析。

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