Double-Encapsulated mRNA Vaccine for COVID-19

适用于 COVID-19 的双囊 mRNA 疫苗

基本信息

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
项目类别：
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

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

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项目摘要

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.

项目摘要 COVID-19是由新型冠状病毒SARS-COV-2引起的多功能疾病，已成为最多的我们一生中有影响力的医疗保健，社会和经济危机。 SARS-COV-2与前两个冠状病毒在21世纪引起了人类爆发，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，但大流行对 2022年4月中旬，全球> 5亿人，造成600万人死亡。如果Covid-19死亡率是更接近SARS和MER的MERS，当前大流行的影响将无与伦比的影响更大灾难性。需要冷藏的需求，对助推器的需求以及不良过敏的潜力反应是当前Covid-19疫苗的主要缺点。为了解决这些缺点，我们建议生成一种在房间稳定的稳定的共vid-19 mRNA疫苗温度只需要一份注入，因此在全国和全球部署疫苗接种运动，不太容易引起超敏反应。我们计划进行此证明在24个月的概念研究中，由一个多学科的工程师，分子病毒学家和免疫学家。我们的总体目标是将编码编码的mRNA分子加倍。磷脂纳米体中的冠状病毒峰蛋白，然后进入可生物降解的聚合物纳米球至维持mRNA释放。我们将表征纳米封装mRNA的抗原性和完整性在纳米封装和涂层之后，并确定确保房间稳定性的最佳过程条件冻干后的温度。我们还将评估安全性，药代动力学和免疫原性纳米囊化的抗原并在两个动物模型中进行挑战研究，以期随后发生临床研究。基于这些研究，我们将选择最佳的纳米成型以进行扩展，更详细在第二阶段的表征，建立效力和释放规格以及法规研究。