A Peptide Nanoparticle Nicotine Vaccine

肽纳米颗粒尼古丁疫苗

• 批准号: 8289967
• 负责人: PETER BURKHARD
• 金额: $ 78.5万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8289967
• 关键词: Adjuvant; Adverse effects; Animal Model; Antibodies; B-Lymphocytes; Binding; Blood; Clinical Research; Clinical Trials; Coupled; Drug Formulations; Engineering; Epitopes; Freeze Drying; Goals; Haplotypes; Haptens; Human; Immune response; Immunization; Intramuscular; Mus; Nicotine; Pain; Patients; Property; Proteins; Protocols documentation; Route; Safety; Stream; Toxic effect; Translations; Vaccines; Work; addiction; density; design; immunogenic; immunogenicity; large scale production; nanoparticle; novel; peptide A; phase 1 study; polypeptide; scaffold

DESCRIPTION (provided by applicant): We have recently developed a novel type of vaccine platform, so-called self-assembling polypeptide nanoparticles (SAPNs). We have demonstrated that these SAPNs are highly immunogenic and induce a strong B cell immune response characterized by high antibody titers without the need of adjuvant. We have engineered and biophysically characterized SAPNs to which activated nicotine hapten molecules can be coupled. Antibodies induced upon immunization with these SAPNs will bind nicotine in the blood stream and hence counteract the addiction-causing effect of nicotine. The overarching goal of the project is to demonstrate safety, tolerability and immunogenicity of the SAPN nicotine vaccine in a clinical trials phase I study. To achieve this goal we propose to first establish the immunogenicity of these nicotine-SAPNs in mice and to optimize their design with respect to the density of the hapten molecules, the SAPN concentration, and the route of immunization to obtain the highest possible antibody titer. Next, we will optimize the SAPNs for human use by engineering pan-DR binding epitopes that are specific for the human haplotypes into the SAPN scaffold. The immunogenicity of the SAPNs will then be verified in a second animal model followed by toxicity testings that will establish a safety profile of the SAPNs. The translation pah will then include protein formulation and lyophilization studies to optimize the long-term storage properties of the SAPNs. Along with the application for Swissmedic approval for clinical studies we will work on a large-scale production protocol of the final vaccine. The vaccine of the present project is adjuvant-free. This will eliminate all adjuvant induced side effects and reduce the pric as it will allow a simple galenic formulation of the vaccine. Since the SAPN-vaccines can be applied intranasally their patient acceptance is expected to be higher than for current vaccine approaches which require painful intramuscular

描述（由申请人提供）：我们最近开发了一种新型疫苗平台，即所谓的自组装多肽纳米颗粒（SAPN）。我们已经证明，这些SAPN是高度免疫原性的，并诱导强烈的B细胞免疫应答，其特征在于高抗体滴度而不需要佐剂。我们已经设计和生物药理学特征的SAPNs，激活的尼古丁半抗原分子可以耦合。用这些SAPN免疫后诱导的抗体将结合血流中的尼古丁，从而抵消尼古丁的成瘾作用。该项目的总体目标是在临床试验I期研究中证明SAPN尼古丁疫苗的安全性、耐受性和免疫原性。为了实现这一目标，我们建议首先建立这些尼古丁-SAPN在小鼠中的免疫原性，并优化它们的设计相对于半抗原分子的密度，SAPN浓度和免疫途径，以获得最高的抗体滴度。接下来，我们将通过将对人类单倍型特异性的泛DR结合表位工程化到SAPN支架中来优化用于人类的SAPN。然后将在第二个动物模型中验证SAPN的免疫原性，然后进行毒性试验，以确定SAPN的安全性特征。然后，翻译方案将包括蛋白质制剂和冻干研究，以优化SAPNs的长期储存特性。沿着Swissmedic批准临床研究的申请，我们将致力于最终疫苗的大规模生产方案。本项目的疫苗不含杀虫剂。这将消除所有佐剂诱导的副作用并降低价格，因为它将允许疫苗的简单盖伦制剂。由于SAP疫苗可以鼻内应用，因此预期其患者接受度高于需要疼痛的肌内注射的当前疫苗方法