Developing a Thermostable SARS-CoV-2 RBD-particle Vaccine

项目摘要 由严重急性呼吸系统综合症引起的2019冠状病毒病全球大流行 冠状病毒2（SARS-CoV-2）在我们的有生之年是前所未有的，并已造成重大的社会，经济和社会问题。 人类的苦难在全球范围内，已有76，858，506例确诊病例，导致1，711，498例死亡， 世界卫生组织报告，截至2020年12月。FDA授权的辉瑞公司（-80 ° C存储）的推出， Moderna（-20 ° C储存）疫苗强调了低必要储存温度带来的挑战。 消除新兴疫苗解决方案的冷链要求可以促进分销， 大大节省了供应链成本。为了克服冷链要求，POP生物技术公司提出 研究其新型疫苗佐剂平台的冻干策略， 颗粒，使用SARS CoV-2刺突（S）蛋白的受体结合结构域（RBD）。我们是其中之一 第一次证明液体形式的RBD颗粒可以有效地增加SARS-CoV-2中和抗体， 与可溶性抗原相比，我们的疫苗平台诱导了良好的颗粒形成- 通过与含有少量钴的脂质体简单混合来表征His标记的抗原 卟啉-磷脂（CoPoP）和临床佐剂单磷酰脂质A和QS-21。CoPoP 脂质体引起在生物介质中稳定的快速抗原颗粒化。在这个合作的第一阶段 根据SBIR提案，我们将评估冻干对 将通过生物化学和生物物理测定评价所得冻干疫苗及其效力 通过小鼠的功能性免疫原性。该项目将评估打破冷链的可行性 这是对下一代粒子疫苗系统的需求，这对资源有限的环境至关重要。 与德克萨斯生物医学研究所（TBRI）合作， 2感染将用于研究冻干RBD颗粒疫苗诱导的保护的热稳定性。 1

PROJECT SUMMARY The coronavirus disease 2019 (COVID-19) global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is unprecedented in our lifetime and has caused major social, economic and human suffering. Globally, there have been 76,858,506 confirmed cases, leading to 1,711,498 deaths as reported by the WHO through December 2020. The rollout of FDA-authorized Pfizer (-80 ˚C storage) and Moderna (-20 ˚C storage) vaccines has highlighted the challenges posed by low requisite storage temperatures. Elimination of cold chain requirements for emerging vaccine solutions could facilitate distribution and provide considerable supply chain cost savings. To overcome cold chain requirements, POP Biotechnologies proposes to investigate a lyophilization strategy for its novel vaccine adjuvant platform that induces spontaneous antigen particles, using the receptor-binding domain (RBD) of the SARS CoV-2 spike (S) protein. We were amongst the first to show that a liquid form of RBD particles potently increases SARS-CoV-2 neutralizing antibodies by orders of magnitude compared to the soluble antigen. Our vaccine platform induces the particle formation of well- characterized his-tagged antigens by simple admixing with liposomes that contain small amounts of cobalt porphyrin-phospholipid (CoPoP) and the clinical adjuvants monophosphoryl lipid A and QS-21. CoPoP liposomes give rise to rapid antigen particleization that is stable in biological media. In this collaborative Phase I SBIR proposal, we will assess the impact of lyophilization on the conformational and thermal stability of the resulting lyophilized vaccine, evaluated by biochemical and biophysical assays, and its efficacy will be assessed by functional immunogenicity in mice. This project will assess the feasibility of breaking the cold-chain requirements for a next-generation particle vaccine system, which could be critical for resource-limited settings. In collaboration with the Texas Biomedical Research Institute (TBRI), a transgenic mouse model for SARS-CoV- 2 infection will be used to study the thermostability on protection induced by the lyophilized, RBD particle vaccine. 1