A Peptide Nanoparticle Nicotine Vaccine

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（SAPNs）。我们已经证明，这些sapn具有高度免疫原性，并诱导强烈的B细胞免疫反应，其特征是高抗体滴度，而不需要佐剂。我们已经设计和生物物理表征了活化尼古丁半抗原分子可以耦合的sapn。这些SAPNs免疫后诱导的抗体将在血液中结合尼古丁，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，我们建议首先在小鼠中建立这些尼古丁-SAPN的免疫原性，并根据半抗原分子密度、SAPN浓度和免疫途径优化它们的设计，以获得尽可能高的抗体效价。接下来，我们将通过将人类单倍型特异性的pan-DR结合表位设计到SAPN支架中来优化SAPN供人类使用。sapn的免疫原性将在第二个动物模型中得到验证，随后进行毒性测试，以确定sapn的安全性。翻译pah将包括蛋白质配方和冻干研究，以优化sapn的长期储存特性。在向瑞士医学委员会申请临床研究批准的同时，我们将制定最终疫苗的大规模生产方案。本项目疫苗不含佐剂。这将消除所有佐剂引起的副作用，并降低价格，因为它将使疫苗的盖伦配方变得简单。由于sapn -疫苗可以鼻内应用，预计患者接受度将高于目前需要疼痛的肌肉注射疫苗的方法

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