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.

项目概要 COVID-19 是由新型冠状病毒 SARS-CoV-2 引起的多器官疾病，已成为最常见的多器官疾病。 我们一生中影响深远的医疗保健、社会和经济危机。 SARS-CoV-2 与以下基因相关： 前两种在21世纪引起人类爆发的冠状病毒是SARS-CoV和MERS-CoV。甚至 尽管 COVID-19 死亡率低于其他两种冠状病毒疾病，但大流行已产生影响， 2022 年 4 月中旬，全球超过 5 亿人死亡，并造成超过 600 万人死亡。如果 COVID-19 死亡率是 与SARS和MERS的情况更接近，当前疫情的影响将是无与伦比的 灾难性的。冷藏的需要、加强剂的要求以及潜在的不良过敏 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，因此在全国和全球范围内部署更加实用 疫苗接种运动，并且不太容易引起过敏反应。我们计划进行此证明- 由工程师、分子病毒学家和专家组成的多学科团队进行了 24 个月的概念研究 免疫学家。我们的首要目标是对编码 mRNA 分子进行双重纳米封装 冠状病毒将蛋白刺入磷脂纳米体中，然后进入可生物降解的聚合物纳米球中 维持 mRNA 释放。我们将在之前表征纳米封装的 mRNA 的抗原性和完整性 并在纳米封装和涂层之后确定确保室温稳定性的最佳工艺条件 冻干后的温度。我们还将评估该药物的安全性、药代动力学和免疫原性。 纳米封装抗原并在两种动物模型中进行挑战研究，以期待后续研究 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 表征、建立效力和释放规格以及第二阶段的监管研究。