Development of a Practical Heroin-HIV Vaccine

描述（由申请人提供）：认识到HIV-1感染与注射海洛因的使用频繁相关，美国军方HIV研究计划（MHRP）和国家药物滥用研究所于2010年发起了一项合作机构间协议，以检查创建实用的抗海洛因疫苗（AHV）和HIV疫苗产品组合的可行性。基于最近对成功的MHRP RV 144泰国试验的多机构免疫相关性分析，该试验表明针对HIV-1 gp 120 V2环的抗体与针对HIV-1感染的保护相关，以及先前的研究表明对海洛因滥用的免疫保护的可行性，MHRP认为，存在一个独特的机会来制造针对HIV-1和海洛因的候选肽疫苗。由于这种合作，现在已经创建了一种安全，廉价，基于海洛因-半抗原-肽，易于制造，强佐剂组合的候选AHV/HIV疫苗产品，该产品已准备好进行预期的I期和II期临床试验的优化和先进的临床前测试。如果成功，预计这种疫苗将提供一种可部署的海洛因疫苗，并将代表创造一种实用和有效的艾滋病毒疫苗的重大进展。主要目的是：（1）优化半抗原-gp 41/gp 120-辅助性T细胞肽-佐剂-载体 通过检查啮齿动物的相对免疫应答，确定了三种替代制剂 海洛因半抗原;（2）在啮齿动物中进行高级临床前免疫原性研究， 研究海洛因和HIV gp 41抗体同种型、亲和力、特异性， gp 120-V2环表位;（3）检测疫苗诱导的抗海洛因抗体，以预防 啮齿动物中药物过量相关的麻醉作用和生理作用的预防 和非人灵长类动物;（4）进行疫苗诱导的中和和其他体外功能分析 来自啮齿类动物和非人灵长类动物的抗HIV抗体;以及（5）证明 为未来I/II期临床研究廉价扩大疫苗生产的可行性。

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 vaccineinduced anti-HIV antibodies from rodents and non-human primates; and (5) demonstrate the feasibility of inexpensive scaled-up vaccine manufacture for future phase I/II clinical studies.