Combined cocaine and HIV vaccine

可卡因和艾滋病毒联合疫苗

• 批准号: 8606078
• 负责人: TIMOTHY J CARDOZO
• 金额: $ 84.75万
• 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/8606078
• 关键词: AIDS/HIV problem; Antibodies; Antibody Formation; Antigens; Award; Biomedical Research; Clinical Trials; Cocaine; Cocaine Users; Crack Cocaine; Data; Drug abuse; Epitopes; Glycoproteins; HIV; HIV vaccine; Intervention; Laboratories; Molecular; National Institute of Drug Abuse; Population; Recording of previous events; Research; Scaffolding Protein; Scientist; Solid; Substance abuse problem; Surface; Technology; Time; Vaccines; Work; base; design; high risk; inner city; programs; public health relevance; substance abuser; transmission process; vaccin protein

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）： 针对大部分 HIV 传播的高危人群是 HIV/AIDS 生物医学研究的主要挑战。药物滥用者是主要的高危人群之一，特别是，内城区的强效可卡因使用者感染艾滋病毒的可能性是非使用者的三倍。我们假设，一种同时产生针对可卡因和艾滋病毒的保护性抗体的疫苗可能会对这些人群产生高效的干预措施。这种疫苗可能是可行的，因为科学家联盟在分析最近的 RV144 试验结果时已经确定了第一个显示出可以防止感染 HIV 的表位（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）中。在过去的几年里，我的实验室开发了一个技术平台，用于从可变环表位（包括 V2 环）引发特异性抗体反应。基于这些数据，我们相信我们可以开发出一种能够引发艾滋病毒保护性抗体的免疫原。巧合的是，我们工作中用于引发这些抗体的相同支架蛋白已在临床试验中成功用作可卡因疫苗。因此，为开发可卡因和艾滋病毒联合疫苗提供了一个先进的起点。这种疫苗将成为艾滋病毒/艾滋病和药物滥用交叉领域的先例分子干预措施，并可能对这两个领域产生变革性影响。在我们的艾滋病毒疫苗免疫原设计工作适应药物滥用问题时，这个拟议的项目与我们实验室目前正在追求的想法和方法有很大的不同，因此这个提案对于 NIDA 先锋派来说是理想的选择艾滋病毒/艾滋病研究奖励计划。