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NIH 资助的性传播感染“基于纳米支架的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。该中心由 科学多样化的协同团队，这将致力于发展新的能力，扩大 应用纳米配制疫苗技术，减轻与 沙眼衣原体。沙眼衣原体（Ct）是最常见的细菌性传播 性传播感染（STI），每年影响超过1.3亿人，是可预防的最常见原因。 全世界失明迫切的公共卫生需要一种疫苗来预防由Ct引起的疾病是显而易见的。 尽管为开发衣原体疫苗做出了相当大的努力，但没有任何进展。虽然研究 显示用Ct主要外膜蛋白（MOMP）免疫可诱导显著的 MOMP相关疫苗的保护、配制和交付仍然是一个主要障碍。该中心将重点 开发和测试一种安全有效的Ct疫苗，克服目前努力的局限性， 使用LLNL纳米脂蛋白颗粒（NLP）技术。NLP是我们可以设计的10-25 nm光盘， 提供了一种独特的前向呈递功能性Ct抗原的途径以及一种用于递送核酸的新工具， acids.我们将评估两种不同类型的纳米制剂与不同的交付技术，而 验证Ct的理想化小鼠激发模型。建立该合作研究中心（CRC）将 进一步整合LLNL基于NLP的纳米技术与亚单位疫苗和核酸的开发 这使得我们能够加速安全有效的Ct疫苗的产生。该中心的努力将 包括三个研究项目，它们将处理疫苗开发各种方法： §项目1将开发基于血清型特异性MOMP形式的亚单位疫苗，以及包括 多态性蛋白，以纳米脂蛋白形式存在。 §项目2将展示核酸编码疫苗的纳米脂蛋白递送。 §项目3将在小鼠模型中验证血清特异性反应，使我们能够改进， 联合收割机，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，和3）免疫学。总体而言，该CRC代表了 一种独特的方法来开发疫苗，以防止由Ct引起的性传播感染（STI）， 在Ct和传染病专家与结构方面的专家之间建立协同合作， 生物学和纳米技术。重要的是，拟议的技术平台将成为根除 目前尚无疫苗的多种传染病。

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.