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

• 批准号: 10458649
• 负责人: Matthew Adrian Coleman
• 金额: $ 191.68万
• 依托单位: LAWRENCE LIVERMORE NATIONAL SECURITY, LLC
• 依托单位国家: 美国
• 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/10458649
• 关键词: Address; Affect; Antigens; Apolipoproteins; Bioinformatics; 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; Persons; 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

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关键需求，我们建议建立NIH 资助的性转移感染性的“基于纳米施加咖啡的衣原体的合作研究中心” 气管疫苗。”，这是LLNL，UCI和UCD之间的协作中心。该中心组成 科学多元化的协同团队将致力于开发扩展的新功能 纳米形成的疫苗技术的应用来缓解与健康相关的健康影响 衣原体沙眼。沙眼衣原体（CT）是性传播的最常见细菌 感染（STI），每年影响超过1.3亿人，是可预防的最常见原因 全球盲目。很明显，公共卫生需要疫苗预防CT引起的疾病。 尽管为开发衣原体疫苗而做出了巨大努力，但没有任何努力。而研究有 表明CT主要外膜蛋白（MOMP）免疫可以诱导显着 保护，配方和与MOMP相关的疫苗的传递仍然是一个重大障碍。这个中心将集中精力 在开发和测试安全有效的CT疫苗，以克服当前努力的局限性 使用LLNL纳米蛋白蛋白颗粒（NLP）技术。 NLP是10-25 nm光盘，我们可以设计的 提供独特的路径，呈现功能性CT抗原以及用于核能输送的新工具 酸。我们将通过不同的递送技术评估两种不同类型的纳米形式，而 验证CT理想化的鼠标挑战模型。建立这个合作研究中心（CRC）将 进一步整合了LLNL基于NLP的纳米技术，并开发了亚基疫苗和核酸 交付，使我们能够加速安全有效的CT疫苗。中心的努力将 包括三个研究项目，该项目将解决疫苗开发的潜水方法： §项目1将根据血清特定形式的MOMP开发亚基疫苗，并包括 多态性蛋白质，以纳米脂蛋白呈现。 §项目2将证明核酸编码疫苗的纳米脂蛋白递送。 §项目3将验证鼠标模型中的血清特定响应，使我们能够完善，可能 结合并应用项目1和2中开发的公式。 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 和统计数据，2）蛋白质的产生和表征，以及3）免疫学。总体而言，此CRC代表 针对CT引起的针对性传播感染（STI）开发疫苗的独特方法 与结构性专家建立CT专家与传染病专家之间的协同合作 生物学和纳米技术。重要的是，拟议的技术平台将构成根除的基础 目前没有疫苗的多种传染病。