Novel Nanovaccines Against Nicotine Addiction

对抗尼古丁成瘾的新型纳米疫苗

• 批准号: 9274420
• 负责人: CHENMING M ZHANG
• 金额: $ 2.15万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274420
• 关键词: Adjuvant; Advanced Development; Adverse effects; Affect; Antibodies; Antibody Affinity; Benchmarking; Binding; Bovine Serum Albumin; Carrier Proteins; Chemicals; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical Trials; Conjugated Carrier; Decision Trees; Dialysis procedure; Diphtheria Toxoid; Disease; Electron Microscope; Enzyme-Linked Immunosorbent Assay; Equilibrium; Evaluation; Glycolates; Goals; Haptens; Health; Human; Immune; Immune response; Keyhole Limpet Hemocyanin; Lead; Lipids; Lipopolysaccharides; Liposomes; Malignant Neoplasms; Medical Societies; Mental Depression; Methods; Modeling; Molecular; Molecular Weight; Mus; National Institute of Drug Abuse; Nature; Nicotine; Nicotine Dependence; Particle Size; Preparation; Process; Proteins; Psychotropic Drugs; Rattus; Reagent; Research; Research Personnel; Safety; Serum; Smoker; Smoking; Social Impacts; Staging; Stroke; Structure; Substance abuse problem; Succinic Acids; Surface; Technology; Testing; Tetanus Toxoid; Tobacco use; United States; Vaccination; Vaccines; base; combat; cross reacting material 197; density; design; economic impact; efficacy testing; experience; immunogenicity; improved; innovation; light scattering; nanoparticle; nanovaccine; novel; particle; protein complex; research study; scaffold; scale up; small molecule; smoking cessation; success; suicidal behavior; transmission process; vaccine candidate

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.

描述（由申请人提供）：一种针对尼古丁成瘾吸烟的新型纳米诺酮是日益增长的全球问题。长期使用烟草被认为是严重疾病的负责因素，例如慢性阻塞性肺部疾病，中风，慢性肺部疾病和癌症。仅美国就有超过6000万吸烟者。尽管需要迫切需要，但寻找解决问题的方法一直是社会和医疗领域的构成挑战。当前的药理疗法在一些严重的副作用（例如具有自杀行为的抑郁症）方面表现出非常有限的成功。另一方面，免疫药物治疗或疫苗接种已成为有前途的选择。但是，所有当前的疫苗均显示出有限的功效，因此无疑需要改善尼古丁疫苗。 在这个项目中，基于概念验证研究（R21DA030083）的巨大成功，我们建议将基于可生物降解的纳米颗粒基于尼古丁的新型纳米酮综合。与所有经过临床试验的尼古丁疫苗不同，我们的纳米酮将通过在可生物降解的纳米颗粒周围组装脂质来构建，并将带有共轭触觉的载体蛋白结合到脂质中。该项目的创新涉及使用可生物降解的纳米颗粒，免疫增强的脂质，专门选择的载体蛋白和纳米酮组装中的分子佐剂。我们预计，通过成功执行精心设计的实验，我们将能够确定一个领先的疫苗候选者，该疫苗将表现出对尼古丁的前所未有的高抗体滴度，并可以将其推进到临床试验中。具有非常协同专业知识的调查人员致力于该项目的成功。该项目的广泛影响在于一种针对尼古丁的新有效疫苗，其潜在的社会和经济影响的潜力，以及一种用于针对其他精神活性药物生产急需的疫苗的平台技术。 我们的目标是开发具有控制尺寸的有效疫苗，该疫苗可以引起对尼古丁的强烈特异性免疫反应，并可以随后进行临床试验。为了实现该目标，提出了以下特定目的：1）PLGA纳米颗粒的制备，2）纳米酮颗粒的组装和3）评估疫苗的免疫原性和生物安全。凭借强大而支持的初步结果和研究人员的集体经验，我们坚信该项目将非常成功，并最终导致有效的疫苗反对尼古丁成瘾。

项目成果

Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction.

• DOI: 10.1016/j.biomaterials.2017.11.021
• 发表时间: 2018-03
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Zhao Z;Harris B;Hu Y;Harmon T;Pentel PR;Ehrich M;Zhang C
• 通讯作者: Zhang C

Multifunctional Nanosystem for Targeted and Controlled Delivery of Multiple Chemotherapeutic Agents for the Treatment of Drug-Resistant Breast Cancer.

• DOI: 10.1021/acsomega.8b00949
• 发表时间: 2018-08-31
• 期刊: ACS omega
• 影响因子: 4.1
• 作者: Lou S;Zhao Z;Dezort M;Lohneis T;Zhang C
• 通讯作者: Zhang C

Effect of Adjuvant Release Rate on the Immunogenicity of Nanoparticle-Based Vaccines: A Case Study with a Nanoparticle-Based Nicotine Vaccine.

佐剂释放速率对纳米颗粒疫苗免疫原性的影响：基于纳米颗粒的尼古丁疫苗的案例研究。

• DOI: 10.1021/acs.molpharmaceut.9b00279
• 发表时间: 2019
• 期刊: Molecular pharmaceutics
• 影响因子: 4.9
• 作者: Zhao,Zongmin;Hu,Yun;Harmon,Theresa;Pentel,Paul;Ehrich,Marion;Zhang,Chenming
• 通讯作者: Zhang,Chenming

A Nano-in-Nano Polymer-Dendrimer Nanoparticle-Based Nanosystem for Controlled Multidrug Delivery.

• DOI: 10.1021/acs.molpharmaceut.7b00219
• 发表时间: 2017-07
• 期刊: Molecular pharmaceutics
• 影响因子: 4.9
• 作者: Zongmin Zhao;Song Lou;Yun Hu;Jie Zhu;Chenming Zhang

The impact of sphingosine kinase inhibitor-loaded nanoparticles on bioelectrical and biomechanical properties of cancer cells.

• DOI: 10.1039/c5lc01201e
• 发表时间: 2016-01-07
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Babahosseini H;Srinivasaraghavan V;Zhao Z;Gillam F;Childress E;Strobl JS;Santos WL;Zhang C;Agah M
• 通讯作者: Agah M