Double-Encapsulated mRNA Vaccine for COVID-19

适用于 COVID-19 的双囊 mRNA 疫苗

• 批准号: 10611763
• 负责人: TREVOR P. CASTOR
• 金额: $ 30万
• 依托单位: APHIOS CORPORATION
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-03 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611763
• 关键词: 2019-nCoV; Acute; Address; Allergic Reaction; Animal Model; Antigens; Biological Sciences; COVID-19; COVID-19 mortality; COVID-19 patient; COVID-19 vaccine; Cessation of life; Clinical Research; Communicable Diseases; Coronavirus; Coronavirus spike protein; Country; Cryopreservation; Development; Disease; Disease Outbreaks; Dose; Drug Kinetics; Economics; Education; Encapsulated; Engineering; Ensure; European Union; Fatality rate; Freeze Drying; Future; Gene Proteins; Goals; Government; Healthcare; Human; Hypersensitivity; Immunologist; In Vitro; Individual; Industry; Injections; Life; Life Expectancy; Lipids; Liquid substance; Measures; Mental Health; Messenger RNA; Middle East Respiratory Syndrome; Middle East Respiratory Syndrome Coronavirus; Minority; Modification; Molecular; Nanosphere; Organ; Persons; Phase; Phospholipids; Polyethylene Glycols; Polymers; Poverty; Prevention strategy; Process; RNA vaccine; Race; Reaction; Reporting; Resolution; SARS coronavirus; Safety; Severe Acute Respiratory Syndrome; Social Distance; Societies; Solvents; Specific qualifier value; Technology; Temperature; Therapeutic; Universities; Vaccination; Vaccines; Viral; Viral Vector; Virus; biodegradable polymer; biological systems; coronavirus disease; coronavirus pandemic; current pandemic; face mask; future pandemic; immunogenicity; in vivo; in vivo evaluation; innovation; mRNA Stability; manufacturability; multidisciplinary; mutant; nanoencapsulated; nanoformulation; nanoparticle; nanopolymer; novel coronavirus; pandemic disease; pandemic impact; pill; pre-pandemic; reconstitution; remdesivir; scale up; social; socioeconomics; vector-based vaccine

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.

项目总结 由新型冠状病毒SARS-CoV-2引起的多器官疾病新冠肺炎已成为全球最大的 我们一生中影响深远的医疗保健、社会和经济危机。SARS-CoV-2在基因上与 21世纪导致人类暴发的前两种冠状病毒，SARS-CoV和MERS-CoV。连 尽管新冠肺炎的死亡率低于其他两种冠状病毒疾病，但这次大流行受到了 2022年4月中旬，全球有5亿人死亡，造成600万人死亡。如果新冠肺炎的死亡率是 与SARS和MERS更接近的是，当前大流行的影响将是无与伦比的 灾难性的。对冷藏的需要，对增强剂的要求，以及不良过敏的可能性 反应，是目前新冠肺炎疫苗的主要缺点。 为了解决这些缺点，我们建议生产一种在室内稳定的新冠肺炎mrna疫苗。 温度，只需要一次注射，因此在全国和全球范围内部署在 疫苗接种活动，不太容易引起过敏反应。我们计划进行这项证明- 为期24个月的概念研究，由工程师、分子病毒学家和 免疫学家。我们的首要目标是双纳米囊化编码 冠状病毒刺突蛋白在磷脂纳米体中，然后进入可生物降解的聚合物纳米球中 维持信使核糖核酸释放。我们将鉴定纳米包裹的信使核糖核酸的抗原性和完整性 并在纳米胶囊化和包衣后，确定确保室温稳定性的最佳工艺条件 冷冻干燥后的温度。我们还将评估该药的安全性、药代动力学和免疫原性。 并在两个动物模型中进行挑战研究，以预测随后的 临床研究。在这些研究的基础上，我们将选择最好的纳米配方进行放大，更详细 表征，建立效力和释放规格，并在第二阶段进行监管研究。