Novel Nanovaccines Against Nicotine Addiction

描述(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主要因素。仅在美国就有6000多万烟民。尽管迫切需要解决这一问题，但如何解决这一问题一直是社会和医疗领域面临的一个持续挑战。目前的药物治疗显示出非常有限的成功和一些严重的副作用，如伴有自杀行为的抑郁症。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效果，因此毫无疑问，对改进的尼古丁疫苗的需求很大。在这个项目中，在概念验证研究(R21DA030083)取得巨大成功的基础上，我们提议合成可生物降解的纳米颗粒为基础的针对尼古丁的新型纳米疫苗。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类来构建，带有共轭半抗原的载体蛋白将偶联到脂类上。该项目的创新包括使用可生物降解的纳米颗粒、免疫增强脂、特定选择的载体蛋白以及在纳米疫苗组装中使用的分子佐剂。我们预计，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，它将显示出前所未有的高尼古丁抗体效价，并可进入临床试验。调查人员凭借出色的协同专业知识，致力于这一项目的成功。该项目的广泛影响在于一种新的有效的尼古丁疫苗的潜力，其潜在的社会和经济影响，以及生产针对其他精神活性药物的迫切需要的疫苗的平台技术。我们的目标是开发一种有效的、大小可控的疫苗，能够引发对尼古丁的强烈特异性免疫反应，并随后可以推进到临床试验。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的评价。凭借强有力和支持性的初步结果以及研究人员的集体经验，我们坚信这个项目将非常成功，并最终导致出现一种有效的尼古丁成瘾疫苗。

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.