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感染的频繁关联与注射的海洛因，美国军事HIV研究计划（MHRP）和美国国家药物滥用研究所在2010年启动了一项合作跨性别协议，以研究创建抗抗疫蛋白疫苗（AHV）和HIV疫苗的实践组合结合性疫苗和HIV疫苗。 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海洛因。由于这项合作，现已创建了一种安全，廉价，基于海洛因 - hapten肽的基于易于制造的，易于制造，辅助组合候选AHV/HIV疫苗产品，已准备好用于预期I期和II期临床试验的优化和先进的临床前测试。如果成功的话，预计这种疫苗将提供可部署的海洛因疫苗，并代表创建实用有效的HIV疫苗的重大进步。主要目标是：（1）优化Hapten-GP41/GP120-T Helper-Adjuvant-Carrier-Crarrer配方，通过检查具有三个替代性铅海洛因触觉的啮齿动物的相对免疫反应； （2）对具有最终铅配方的啮齿动物进行晚期临床前免疫原性研究，以检查抗体同种型，亲和力，海洛因和HIV GP41和GP120-V2环路epopopes的特异性； （3）检查疫苗诱导的抗英雄蛋白抗体，以预防麻醉作用并预防与啮齿动物和非人类灵长类动物中药物过量相关的生理作用； （4）对疫苗I进行中和和其他体外功能分析