Center for Biologically Inspired Nano-scaffolds for Mitigating Chlamydia trachomatis Pathogenesis

减轻沙眼衣原体发病机制的生物启发纳米支架中心

基本信息

批准号：
10223108
负责人：
Matthew Adrian Coleman
金额：
$ 199.56万
依托单位：
UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-08 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10223108
关键词：
Address Affect Antigens Apolipoproteins Bioinformatics Biological Blindness California Chlamydia trachomatis Collaborations Communicable Diseases Development Disease Engineering Formulation Fostering Funding Generations Health Immunization Immunology Infection Interdisciplinary Study Laboratories Methodology Modeling Mus Nanotechnology Nucleic Acid Vaccines Pathogenesis Pathology Production Proteins Public Health Research Research Personnel Research Project Grants STI prevention Scientist Sexual Transmission Sexually Transmitted Diseases Structure Students Subunit Vaccines Techniques Technology Testing United States National Institutes of Health Universities Vaccines Work base career development direct application industry partner major outer membrane protein model development mouse model nano nanoformulation nanolipoprotein particles nonhuman primate novel nucleic acid delivery pathogen preservation prevent response scaffold statistics structural biology success technology development tool vaccine development

项目摘要

Abstract In order to address the critical need for a Chlamydia trachomatis vaccine, we propose to establish the NIH funded Sexually Transferred Infectious “Cooperative Research Center for NanoScaffold-Based Chlamydia trachomatis Vaccines.”, which is a collaborative center between LLNL, UCI and UCD. The Center is composed of scientifically diverse synergistic teams, which will be dedicated to developing new capabilities for expanding the application of nano-formulated vaccine technologies for mitigating health effects associated with Chlamydia trachomatis. Chlamydia trachomatis (Ct)is the most common bacterial sexually transmitted infection (STI), affecting over 130 million people every year, and is the most common cause of preventable blindness worldwide. The pressing public health need for a vaccine to prevent diseases caused by Ct is clear. Despite considerable efforts to develop a chlamydial vaccine, none have been forthcoming. While studies have shown that immunization with the Ct major outer membrane protein (MOMP) can induce significant protection, formulation and delivery of MOMP-related vaccines remains a major hurdle. This Center will focus on developing and testing a safe and efficacious Ct vaccine that overcomes the limitations of current efforts using LLNL nanolipoprotein particle (NLP) technology. NLPs are 10-25 nm disc we can engineer that will provide a unique path forward presenting functional Ct antigens as well as a novel tool for delivery of nucleic acids. We will evaluate two different types of nano-formulations with different delivery techniques, while validating an idealized mouse challenge model for Ct. Establishing this Cooperative Research Center (CRC) will further integrate LLNL's NLP-based nanotechnology with development of subunit vaccines and nucleic acid delivery, enabling us to accelerate the generation of a safe and efficacious Ct vaccine. The Center's efforts will include three research projects, which will tackle diverse approaches to vaccine development: § Project 1 will develop subunit vaccines based on serovar-specific forms of MOMP, as well as include polymorphic proteins, presented in nanolipoproteins. § Project 2 will demonstrate nanolipoprotein delivery of nucleic acid–encoded vaccines. § Project 3 will validate serovar-specific responses in mouse models, enabling us to refine, possibly combine, and apply formulations developed in Projects 1 and 2. The research projects will be supported by the Administrative Core and three scientific cores: 1) Bioinformatics and Statistics, 2) Protein Production and Characterization, and 3) Immunology. Overall, this CRC represents a unique approach to the development of vaccines against sexually transmitted infections (STIs) caused by Ct by establishing synergistic collaborations between experts in Ct and infectious disease with experts in structural biology and nanotechnology. Importantly, the proposed technology platform will form the basis for eradicating multiple infectious disease for which no vaccine is currently available.

抽象的为了满足对沙眼衣原体疫苗的迫切需求，我们建议建立 NIH 资助性传播传染病“纳米支架衣原体合作研究中心” 沙眼疫苗。”，这是 LLNL、UCI 和 UCD 之间的合作中心。科学多样化的协同团队，将致力于开发新的能力，以扩大应用纳米制剂疫苗技术来减轻与以下疾病相关的健康影响沙眼衣原体 (Ct) 是最常见的性传播细菌。感染（STI），每年影响超过 1.3 亿人，是可预防疾病的最常见原因显然，公共卫生领域迫切需要一种疫苗来预防 Ct 引起的疾病。尽管为开发衣原体疫苗付出了巨大努力，但尚未取得进展。研究表明，用 Ct 主要外膜蛋白 (MOMP) 进行免疫可以诱导显着的 MOMP 相关疫苗的保护、配制和交付仍然是该中心将重点关注的一个主要障碍。开发和测试一种安全有效的 Ct 疫苗，克服当前努力的局限性使用 LLNL 纳米脂蛋白颗粒 (NLP) 技术，我们可以设计出 10-25 nm 的 NLP。提供了呈递功能性 Ct 抗原的独特途径以及用于递送核酸的新工具我们将评估具有不同递送技术的两种不同类型的纳米制剂，同时验证 Ct 的理想小鼠挑战模型建立该合作研究中心 (CRC) 将进一步将LLNL基于NLP的纳米技术与亚单位疫苗和核酸的开发相结合交付，使我们能够加速生产安全有效的 Ct 疫苗。包括三个研究项目，将解决疫苗开发的多种方法： § 项目 1 将开发基于 MOMP 血清型特异性形式的亚单位疫苗，并包括多态性蛋白质，存在于纳米脂蛋白中。 § 项目 2 将演示核酸编码疫苗的纳米脂蛋白递送。 § 项目 3 将验证小鼠模型中的血清型特异性反应，使我们能够改进，可能结合并应用项目 1 和 2 中开发的配方。研究项目将得到行政核心和三个科学核心的支持：1）生物信息学和统计学，2) 蛋白质生产和表征，以及 3) 免疫学总体而言，该 CRC 代表了一个。开发针对 Ct 引起的性传播感染 (STI) 疫苗的独特方法在CT和传染病领域的专家与结构领域的专家之间建立协同合作重要的是，所提出的技术平台将构成根除的基础。目前尚无疫苗的多种传染病。