Delivery and Adjuvantation of Nicotine Vaccine by Laser Illumination

激光照明尼古丁疫苗的递送和佐剂

• 批准号: 8999625
• 负责人: Xinyuan Chen
• 金额: $ 24.85万
• 依托单位: UNIVERSITY OF RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8999625
• 关键词: APC Vaccine; Abstinence; Address; Adjuvant; Adverse effects; Affinity; Agonist; Antibodies; Antibody Formation; Antigen-Presenting Cells; Antigens; Area; Award; Binding; Blood Circulation; Brain; Cell Maturation; Clinic; Clinical; Cocaine; Collaborations; Cosmetics; Cutaneous; Data; Dendritic Cells; Development; Drug Addiction; Drug Formulations; Drug abuse; Encapsulated; Ensure; Excipients; Family suidae; Foundations; Future; Glycolates; Goals; Health Sciences; Heroin; Human; Human Resources; Immune response; Immunization; Inferior; Injection of therapeutic agent; Intramuscular; Keyhole Limpet Hemocyanin; Langerhans cell; Lasers; Lighting; Lipid A; Medical; Mentors; Modeling; Mus; Muscle; Nanotechnology; National Institute of Drug Abuse; Needles; Nicotine; Nicotine Dependence; Ovalbumin; Painless; Particulate; Pattern; Pharmacology; Phase I Clinical Trials; Placebos; Polymers; Population; Reaction; Reporting; Research Personnel; Safety; Scientist; Serum; Skin; Smoker; Solid; Strategic Planning; Surface; Technology; Time; Tissues; Topical application; Toxic effect; Training; Translational Research; Vaccine Adjuvant; Vaccines; addiction; aluminum sulfate; base; career; clinical efficacy; compliance behavior; early onset; effective therapy; experience; immunogenicity; improved; influenza virus vaccine; intradermal injection; multidisciplinary; nanoparticle; novel; novel strategies; particle; pre-clinical; research clinical testing; response; restoration; seasonal influenza; small molecule; toll-like receptor 4; vaccine delivery

This K99/R00 proposal seeks highly safe and efficient strategies to improve nicotine vaccine immunogenicity. Treatment of nicotine addiction remains an unmet medical need and nicotine vaccines evolve as a safe and effective therapy to treat nicotine addiction by induction of a relatively long-term abstinence rate with fewer side effects. Yet, only a small fraction of smokers respond to this therapy even after 5-7 monthly immunizations. Enhancing nicotine vaccine immunogenicity remains the key to increase the clinical response rate due to the positive correlation between serum anti-nicotine antibody (NicAb) titer and abstinence rate. An ablative fractional laser (AFL)-based, particulate vaccine and adjuvant-coated transdermal patch is proposed for nicotine vaccine delivery and adjuvantation. The AFL generates self-renewable microchannels (MCs) that provide free paths for vaccine delivery into the skin. Additionally, the AFL possesses superior “built-in” adjuvant effects that are more potent than the majority of traditional adjuvants by induction of antigen presenting cell recruitment and long-term antigen depot. Encapsulation of nicotine vaccine and a safe cutaneous monophosphoryl lipid A (MPL) adjuvant into mixed poly(D,L-lactic-co-glycolic acid) (PLGA) particles with different sizes is expected to simulate a prime/boost immunization and induce the highest and prolonged NicAb titer and “completely” block nicotine entry into the brain. The novel immunization is also expected to improve patient compliance by elimination of needle injection and induce an early-onset and long-lasting immune response. The novel immunization combines AFL, MPL adjuvant, and PLGA polymers already in the clinic to profoundly improve nicotine vaccine immunogenicity and is expected to gain FDA approval for clinical test if sufficient safety and efficacy data can be obtained from this study. Three specific aims are proposed: 1. Optimize AFL-based patch vaccine delivery, 2 & 3. Evaluate nicotine vaccine immunogenicity in mice (2) and miniature pigs (3). These aims will be achieved through courseworks at Harvard-MIT Division of Health Science and through multidisciplinary mentoring and collaboration with well-established scientists. This application fulfills one of the four major goals “Treatment” and the objective “To develop treatments for drug abuse and addiction in association with comorbid conditions” stated in 2010 NIDA strategic plan, and also addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-DA-101, Novel Approaches to Improve Immunogenicity of Vaccine against Small Molecules. The novel immunization strategy will have a broad impact on delivery and adjuvantation of not only nicotine vaccine, but also other anti- addiction vaccines (e.g., cocaine and heroin vaccines) under development and seasonal influenza vaccines in the clinic. Completion of this project will provide the candidate sufficient experience and a superior technology for transition to an independent researcher career in vaccine delivery and adjuvantation field.

该K99/R00提案寻求高度安全有效的策略来改善尼古丁疫苗免疫原性。 尼古丁成瘾的治疗仍然是未满足的医疗需求，尼古丁疫苗作为安全和 通过诱导相对长期的禁欲率，有效地治疗尼古丁成瘾的疗法 效果。然而，即使在每月5-7个月度免疫接种后，也只有一小部分吸烟者对这种疗法做出反应。 增强尼古丁疫苗免疫原性仍然是提高由于 血清抗雪Nicotine抗体（NICAB）滴度和节制率之间的正相关。烧烤 提出了基于分数激光（AFL）的颗粒疫苗和调节涂层的变换贴片 尼古丁疫苗输送和调整。 AFL生成可自我再生的微通道（MCS） 提供疫苗输送到皮肤的自由路径。此外，AFL具有卓越的“内置”可调 通过诱导抗原呈现细胞，比大多数传统调节器更有潜力的效果 招募和长期抗原仓库。尼古丁疫苗和安全皮肤的封装 单磷酸脂质A（MPL）与混合聚（D，L-乳酸 - 乙醇酸）（PLGA）（PLGA）颗粒调节 预计不同尺寸将模拟素数/增强免疫，并诱导最高和延长的NICAB 滴度和“完全”阻止尼古丁进入大脑。新颖的免疫也有望改善 通过消除针头注射并诱导早期发作和持久的免疫力来遵守患者 回复。新型免疫组合AFL，MPL调节和PLGA聚合物已经在诊所中 深刻改善尼古丁疫苗免疫原性，并有望获得FDA批准以进行临床测试 可以从这项研究中获得足够的安全性和效率数据。提出了三个具体目标：1。 优化基于AFL的斑块疫苗输送，2＆3。评估小鼠尼古丁疫苗免疫原性（2）和 微型猪（3）。这些目标将通过哈佛 - 梅特卫生部的课程工程实现 科学以及通过跨学科的指导和与成熟的科学家合作。这 应用程序实现了四个主要目标“治疗”和“开发药物治疗方法的目标之一 与合并条件相关的虐待和成瘾”在2010年NIDA战略计划中说，也 解决广泛的挑战领域（15）转化科学和特定挑战主题，15-DA-101，小说 改善疫苗对小分子的免疫原性的方法。新颖的免疫策略 将对不仅尼古丁疫苗的输送和调整产生广泛的影响，还会对 正在开发的成瘾疫苗（例如可卡因和海洛因疫苗）和季节性影响疫苗 诊所。该项目的完成将为候选人提供足够的经验和卓越的技术 过渡到疫苗输送和调整领域的独立研究人员职业。