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

摘要 为了解决沙眼衣原体疫苗的迫切需求，我们建议建立国家卫生研究院 资助的“性传播传染病”纳米支架衣原体合作研究中心 这是LLNL、UCI和UCD之间的合作中心。该中心由 科学多样的协同团队，将致力于开发新的能力，以扩大 应用纳米配方疫苗技术减轻与以下疾病相关的健康影响 沙眼衣原体。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，是可预防的最常见原因 世界范围内的失明。显然，公共卫生迫切需要一种疫苗来预防由CT引起的疾病。 尽管在开发衣原体疫苗方面做出了相当大的努力，但没有一项即将到来。虽然研究表明 结果表明，Ct主要外膜蛋白(MOMP)免疫小鼠可显著诱导 与MOMP相关的疫苗的保护、配制和交付仍然是一个主要障碍。这个中心将专注于 克服当前工作局限性的安全有效的CT疫苗的研制和试验 采用LLNL纳米脂蛋白颗粒(NLP)技术。NLP是10-25 nm的光盘，我们可以设计它 提供了一种呈现功能性CT抗原的独特途径以及一种用于运送核的新工具 酸。我们将评估两种不同类型的纳米配方，使用不同的输送技术，而 验证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，使我们能够加快安全有效的CT疫苗的产生。该中心的努力将 包括三个研究项目，这些项目将解决疫苗开发的不同方法： §项目1将根据特定于血清的MOMP形式开发亚单位疫苗，并包括 多态蛋白质，存在于纳米脂蛋白中。 项目2将演示纳米脂蛋白对核酸编码疫苗的输送。 §项目3将在小鼠模型中验证特定于血清的反应，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)蛋白质生产和特性，以及3)免疫学。总体而言，这个CRC代表了一个 用独特的方法开发由CT引起的性传播感染(STI)疫苗 建立CT和传染病专家与结构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 目前还没有疫苗可用的多种传染病。

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.