Novel Nanovaccines Against Nicotine Addiction

描述（由申请人提供）：一种针对尼古丁成瘾的新型纳米疫苗吸烟是一个日益严重的全球性问题。长期使用烟草被认为是慢性阻塞性肺病、中风、慢性肺病和癌症等严重疾病的一个责任因素。仅在美国就有6000多万吸烟者。尽管迫切需要，但找到解决问题的方法一直是社会和医学领域的一个持续挑战。目前的药物治疗已经显示出非常有限的成功与一些严重的副作用，如抑郁症与自杀行为。另一方面，免疫药物疗法或疫苗接种已成为一种有前途的替代方案。然而，目前所有的疫苗都显示出有限的功效，因此无疑强烈需要改进的尼古丁疫苗。 在该项目中，基于概念验证研究（R21DA030083）的巨大成功，我们建议合成基于可生物降解纳米颗粒的新型尼古丁纳米疫苗。与所有已经通过临床试验的尼古丁疫苗不同，我们的纳米疫苗将通过在可生物降解的纳米颗粒周围组装脂质来构建，并且具有缀合半抗原的载体蛋白将与脂质缀合。该项目的创新涉及使用可生物降解的纳米颗粒，免疫增强脂质，特别选择的载体蛋白和分子佐剂组装纳米疫苗。我们希望，通过成功执行精心设计的实验，我们将能够确定一种领先的候选疫苗，该疫苗将显示出前所未有的高尼古丁抗体滴度，并可进入临床试验。研究人员，具有卓越的协同专业知识，致力于这个项目的成功。该项目的广泛影响在于开发一种新的有效尼古丁疫苗的潜力，其潜在的社会和经济影响，以及生产急需的其他精神活性药物疫苗的平台技术。 我们的目标是开发一种有效的疫苗，其大小可控，可以引起对尼古丁的强烈特异性免疫反应，并随后进入临床试验。为了实现这一目标，提出了以下具体目标：1）PLGA纳米颗粒的制备，2）纳米疫苗颗粒的组装，3）疫苗的免疫原性和生物安全性评价。有了强有力的初步结果和研究人员的集体经验，我们坚信这个项目将非常成功，并最终导致一种有效的尼古丁成瘾疫苗的出现。

DESCRIPTION (provided by applicant): A novel nanovaccine against nicotine addiction smoking is a growing global problem. Chronic use of tobacco is considered a responsible factor for serious diseases such as chronic obstructive pulmonary disease, stroke, chronic lung disease, and cancer. There are more than 60 million smokers in the U.S alone. Despite the urgent need, finding ways to combat the problem has been a constant challenge to the society and the medical field. Current pharmacological therapies have shown very limited success with some serious side-effects, such as depression with suicidal behavior. On the other hand, immunopharmacotherapy or vaccination has emerged as a promising alternative. However, all current vaccines have shown limited efficacy, and thus there is undoubtedly a strong need for improved nicotine vaccines. In this project, building on the tremendous success of a proof-of-concept study (R21DA030083), we propose to synthesize biodegradable nanoparticle based novel nanovaccines against nicotine. Different from all nicotine vaccines that have gone through clinical trials, our nanovaccines will be constructed by assembling lipids around biodegradable nanoparticles, and the carrier proteins with conjugated haptens will be conjugated to the lipids. The innovation of this project involves the use of the biodegradable nanoparticle, immune enhancing lipids, specifically selected carrier proteins, and a molecular adjuvant in the assembly of the nanovaccines. We expect that, through successfully executing the carefully designed experiments, we will be able to identify a leading vaccine candidate that will show unprecedentedly high antibody titers against nicotine and can be advanced into clinical trials. The investigators, with superbly synergizing expertise, are committed to the success of this project. The broad impact of this project resides in the potential of a new and effective vaccine against nicotine, its potential social and economic impact, and a platform technology for producing much needed vaccines against other psychoactive drugs. Our goal is to develop an effective vaccine with controlled size that can elicit strong specific immune response toward nicotine and can be subsequently advanced to clinical trials. To achieve the goal, the following specific aims are proposed: 1) preparation of PLGA nanoparticles, 2) assembly of nanovaccine particles, and 3) evaluation of the immunogenicity and biosafety of the vaccines. With the strong and supportive preliminary results and the collective experiences of the investigators, we strongly believe this project will be extremely successful and eventually lead to the emergence of an effective vaccine against nicotine addiction.