Combined cocaine and HIV vaccine

可卡因和艾滋病毒联合疫苗

• 批准号: 8884699
• 负责人: TIMOTHY J CARDOZO
• 金额: $ 6.53万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8884699
• 关键词: AIDS/HIV problem; Address; Antibodies; Antibody Formation; Antigens; Award; Biomedical Research; Clinical Trials; Cocaine; Cocaine Users; Crack Cocaine; Data; Drug abuse; Epitopes; Glycoproteins; HIV; HIV Infections; HIV vaccine; Health; Intervention; Laboratories; Molecular; National Institute of Drug Abuse; Population; Recording of previous events; Research; Scaffolding Protein; Scientist; Self Administration; Solid; Substance abuse problem; Surface; Technology; Time; Vaccines; Work; base; design; high risk; inner city; programs; scaffold; substance abuser; transmission process

DESCRIPTION (provided by applicant): Targeting the high-risk groups that are responsible for most of the transmission of HIV is a major challenge in biomedical research on HIV/AIDS. Substance abusers are one of the key high-risk groups, and, specifically, inner city crack cocaine users are three times more likely than non-users to be infected with HIV. We hypothesize that a vaccine that raises protective antibodies simultaneously to both cocaine and HIV could be a high-impact intervention in these populations. Such a vaccine may be feasible, because the first epitopes shown to protect against the acquisition of HIV have been identified by a consortium of scientists analyzing the results of the recent RV144 trial (Haynes et. al. NEJM 2012). Their analysis showed that the protective epitopes are located in the second variable loop (V2 loop) of the surface envelope glycoprotein of the HIV virus. Over the past few years, my laboratory has developed a technology platform for eliciting specific antibody responses from variable loop epitopes, including the V2 loop. Based on these data, we believe that we can develop an immunogen capable of eliciting HIV-protective antibodies. By coincidence, the same scaffold protein used to elicit these antibodies in our work has been used successfully as a cocaine vaccine in a clinical trial. Thus, an advanced starting point is present to develop a combined cocaine and HIV vaccine. Such a vaccine would be a precedent-setting molecular intervention at the intersection of HIV/AIDS and substance abuse, and may have a transformative effect on both fields. In the adaptation of our HIV vaccine immunogen design work to the problem of drug abuse, this proposed project represents a significant departure from the ideas and approaches that are currently being pursued in the our lab, so this proposal is ideal for the NIDA Avante-Garde Award Program for HIV/AIDS Research.

描述（由申请人提供）：针对艾滋病毒传播的高危人群是艾滋病毒/艾滋病生物医学研究的主要挑战。药物滥用者是关键的高危群体之一，具体而言，市中心快克可卡因使用者感染艾滋病毒的可能性是非吸毒者的三倍。我们假设，一种同时提高对可卡因和艾滋病毒的保护性抗体的疫苗可能是对这些人群的高影响干预。这种疫苗可能是可行的，因为一个科学家联盟在分析最近的RV144试验结果后，已经确定了第一批显示可防止获得艾滋病毒的抗原表位（Haynes等人，NEJM 2012）。他们的分析表明，保护性表位位于HIV病毒表面包膜糖蛋白的第二个可变环（V2环）。在过去的几年中，我的实验室开发了一种技术平台，用于从包括V2环在内的可变环表位中激发特异性抗体反应。基于这些数据，我们相信我们可以开发出一种能够激发hiv保护性抗体的免疫原。巧合的是，在我们的研究中用于引发这些抗体的支架蛋白在临床试验中被成功地用作可卡因疫苗。因此，为研制可卡因和艾滋病毒联合疫苗提供了一个先进的起点。这种疫苗将是在艾滋病毒/艾滋病和药物滥用交叉领域开创先例的分子干预，并可能对这两个领域产生变革性影响。在将我们的HIV疫苗免疫原设计工作应用于药物滥用问题的过程中，这个提议的项目与我们实验室目前所追求的想法和方法有很大的不同，因此这个提议是NIDA HIV/AIDS研究先锋奖项目的理想选择。