Double-Encapsulated mRNA Vaccine for COVID-19

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.