Novel Nanovaccines Against Nicotine Addiction

描述（由申请人提供）：一种对抗尼古丁成瘾的新型纳米疫苗是一个日益严重的全球性问题。长期使用烟草被认为是导致慢性阻塞性肺病、中风、慢性肺病和癌症等严重疾病的一个负责因素。仅在美国就有6000多万烟民。尽管迫切需要，但寻找解决这一问题的方法一直是社会和医学界面临的一项挑战。目前的药物治疗已经显示出非常有限的成功和一些严重的副作用，如抑郁症和自杀行为。另一方面，免疫药物疗法或疫苗接种已成为一种有希望的替代方案。然而，目前所有的疫苗都显示出有限的功效，因此毫无疑问，迫切需要改进尼古丁疫苗。在本项目中，基于一项概念验证研究（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。与所有经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，并将带有偶联半抗原的载体蛋白偶联到脂质上。该项目的创新之处包括在纳米疫苗的组装中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。我们期望，通过成功地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抗尼古丁抗体滴度，并可以推进临床试验。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。这一项目的广泛影响在于有可能研制出一种新的有效的尼古丁疫苗，其潜在的社会和经济影响，以及一种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，其大小可以控制，可以引发对尼古丁的强烈特异性免疫反应，随后可以进行临床试验。为此，提出了以下具体目标：1)制备PLGA纳米颗粒；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。有了强有力的和支持性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，并最终导致对抗尼古丁成瘾的有效疫苗的出现。

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.