Combined cocaine and HIV vaccine

描述（由申请人提供）：针对高危人群，负责大多数艾滋病毒的传播是一个重大的挑战，在生物医学研究艾滋病毒/艾滋病。药物滥用者是主要的高风险群体之一，具体而言，市中心的快克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，一种同时针对可卡因和艾滋病毒产生保护性抗体的疫苗可能是这些人群的高影响干预措施。这样的疫苗可能是可行的，因为已经由分析最近RV 144试验的结果的科学家联盟鉴定了显示出防止HIV获得的第一个表位（Haynes et. 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HIV保护性抗体的免疫原。巧合的是，在我们的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地用作可卡因疫苗。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一种开创先例的分子干预措施，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的适应药物滥用的问题，这个拟议的项目代表了一个显着偏离的想法和方法，目前正在追求在我们的实验室，所以这个建议是理想的NIDA Avante-Garde奖计划的艾滋病毒/艾滋病研究。

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.