Combined cocaine and HIV vaccine

描述(由申请人提供)：针对造成艾滋病毒大部分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。吸毒者是关键的高危群体之一，具体地说，市中心吸食可卡因的人感染艾滋病毒的可能性是不吸食可卡因的人的三倍。我们假设，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力干预。这样的疫苗可能是可行的，因为一个科学家联盟分析了最近的RV144试验(Haynes et.艾尔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，可以从可变环表位(包括V2环)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诱导HIV保护性抗体的免疫原。巧合的是，在我们的工作中用来诱导这些抗体的同一支架蛋白已经在临床试验中成功地用作可卡因疫苗。因此，开发可卡因和艾滋病毒联合疫苗是一个较高的起点。这种疫苗将在艾滋病毒/艾滋病和药物滥用的交叉点上开创分子干预的先例，并可能对这两个领域产生变革性的影响。在使我们的HIV疫苗免疫原设计工作适应药物滥用问题的过程中，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，因此这个建议非常适合NIDA艾滋病毒/艾滋病研究Avante-Garde奖计划。

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.