Peptide-vaccine development against Lyme disease Supplement

项目摘要 莱姆病是一种地方性蜱传疾病，与关节炎等衰弱表现相关， 肌肉疼痛、心脏炎、脑膜炎和脑脊髓炎。尽管在这一领域作出了广泛努力， 预防这种感染的疫苗可供人类使用。为了解决这个问题，我们的实验室 开发了新的方法来鉴定蜱和哺乳动物细菌感染期间相关的抗原， 基于这些蛋白质的胞外和保守区域设计肽抗原。通过工作 在母申请中提出的，我们选择和评估表达在 B的地方性流行周期的各个阶段。作为莱姆病疫苗抗原。这是目前 使用基于肽和重组蛋白的疫苗进行。在本附录中，我们建议扩大 将疫苗制剂转移到mRNA疫苗平台。我们已经找到了可以产生mRNA的合作伙伴 构建体编码感兴趣的抗原，并将它们包封在世界级临床级脂质纳米颗粒中。 我们将首先验证mRNA技术的体外和体内表达和免疫原性，并进行 与肽和重组制剂的头对头比较。我们将使用兽用莱姆疫苗 以供比较。在这项工作的结论，我们将评估一个新的平台莱姆疫苗 开发并生成必要的临床前数据，以便能够过渡到开发的临床研究 莱姆病的疫苗。

Project Summary Lyme disease is an endemic tick-borne disease associated with debilitating manifestations such as arthritis, muscle pain, carditis, meningitis, and encephalomyelitis. Despite extensive efforts in the field, there is still no vaccine for the prevention of this infection available for human use. To address this problem, our laboratory has developed novel methodologies to identify antigens relevant during bacterial infection in ticks and mammals and design peptide antigens based on extracellular and conserved regions of these proteins. Through the work proposed in the parent application, we are selecting and evaluating outer-membrane proteins expressed in various phases of the enzootic cycle of B. burgdorferi as vaccine antigens against Lyme disease. This is currently performed using peptide and recombinant protein-based vaccines. In this supplement, we propose to expand vaccine formulations to the mRNA vaccine platform. We have secured partners that will generate mRNA constructs encoding the antigens of interest and encase them in world class clinical grade lipid nanoparticles. We will first validate the mRNA technology for in vitro and in vivo expression and immunogenicity, and perform head-to-head comparisons with the peptide and recombinant formulations. We will use veterinary Lyme vaccines for comparison. At the conclusion of this work, we will have evaluated a novel platform for Lyme vaccine development and generated essential pre-clinical data to enable transition to clinical studies for the development of a vaccine against Lyme disease in humans.