Double-Encapsulated mRNA Vaccine for COVID-19

项目摘要 COVID-19是由新型冠状病毒SARS-CoV-2引起的多器官疾病，已成为世界上最严重的疾病。 影响我们一生的医疗、社会和经济危机。SARS-CoV-2在基因上与 前两种在21世纪世纪引起人类疫情的冠状病毒，SARS-CoV和MERS-CoV。甚至 尽管COVID-19的死亡率低于其他两种冠状病毒疾病，但大流行已经影响到， 2022年4月中旬，全球超过5亿人，造成超过600万人死亡。如果COVID-19死亡率 与SARS和MERS相比，当前大流行的影响将无与伦比地多 灾难性的需要冷藏，需要加强剂，以及潜在的不良过敏反应 反应是当前COVID-19疫苗的主要缺点。 为了解决这些缺点，我们建议生产一种在室温下稳定的COVID-19 mRNA疫苗， 温度，只需要一次注射，因此在国家和全球范围内部署更实际。 疫苗接种运动，并不容易引起过敏反应。我们计划进行这一证明- 由工程师、分子病毒学家和生物学家组成的多学科团队进行了为期24个月的概念研究， 免疫学家我们的首要目标是将编码基因的mRNA分子双重纳米封装起来， 冠状病毒刺突蛋白在磷脂纳米体，然后进入可生物降解的聚合物纳米球， 持续mRNA释放。我们将表征纳米封装mRNA的抗原性和完整性， 并确定确保室温下稳定性的最佳工艺条件 冷冻干燥后的温度。我们还将评估药物的安全性、药代动力学和免疫原性。 纳米封装的抗原，并在两种动物模型中进行攻击研究，以预期随后的 临床研究。基于这些研究，我们将选择最佳的纳米制剂进行放大，更详细地 在II期进行特性鉴定、建立效价和放行质量标准以及监管研究。

PROJECT SUMMARY COVID-19, the multiorgan disease caused by the novel coronavirus SARS-CoV-2, has become the most impactful healthcare, social, and economic crisis of our lifetime. SARS-CoV-2 is genetically related to the previous two coronaviruses that caused human outbreaks in the 21st century, SARS-CoV and MERS-CoV. Even though COVID-19 mortality is lower than the other two coronavirus diseases, the pandemic has impacted, by mid-April 2022, >500 million people worldwide, and caused >6 million deaths. Had the COVID-19 mortality been closer to those of SARS and MERS, the impact of the current pandemic would be incomparably more catastrophic. The need for cold storage, the requirement for boosters, and the potential for adverse allergic reactions, are major drawbacks of current COVID-19 vaccines. To address these shortcomings, we propose to generate a COVID-19 mRNA vaccine that is stable at room temperature, requires only one injection, thus being more practical to deploy nationally and globally during vaccination campaigns, and is less prone to cause hypersensitivity reactions. We plan to conduct this Proof-of- Concept study over a 24-month period with a multidisciplinary team of engineers, molecular virologists, and immunologists. Our overarching goal is to double nanoencapsulate the mRNA molecule that encodes the coronavirus Spike protein in phospholipid nanosomes and then into biodegradable polymer nanospheres to sustain mRNA release. We will characterize the antigenicity and integrity of the nanoencapsulated mRNA before and after nanoencapsulation and coating and determine the best process conditions that ensure stability at room temperature after lyophilization. We will also evaluate the safety, pharmacokinetics, and immunogenicity of the nanoencapsulated antigen and perform challenge studies in two animal models, in anticipation of subsequent clinical studies. Based on these studies, we will select the best nanoformulation for scale-up, more detailed characterization, establish potency and release specifications, and regulatory studies in Phase II.