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

开发耐热 SARS-CoV-2 RBD 颗粒疫苗

• 批准号: 10448469
• 负责人: Wei-chiao Huang
• 金额: $ 30万
• 依托单位: POP BIOTECHNOLOGIES, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-09 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10448469
• 关键词: 2019-nCoV; ACE2; Adjuvant; Agonist; Animal Model; Antibodies; Antibody Response; Antigens; Authorization documentation; Binding; Biochemical; Biological; Biological Assay; Biomedical Research; Biophysics; Biotechnology; COVID-19; COVID-19 pandemic; COVID-19 vaccine; Cessation of life; Chemicals; Clinical; Cobalt; Cold Chains; Collaborations; Cost Savings; Data; Dose; Economics; Emergency Situation; Formulation; Freeze Drying; Freezing; High temperature of physical object; Human; Immunization; Immunize; Immunoglobulin G; Infection; Inflammasome; Institution; Intramuscular; K-18 conjugate; Lipid A; Liposomes; Liquid substance; Measures; Molecular Conformation; Mus; Peer Review; Phase; Phospholipids; Porphyrins; Protein Engineering; QS21; Recombinants; Reporting; Research; Research Institute; Resource-limited setting; Risk; SARS-CoV-2 infection; SARS-CoV-2 spike protein; Serum; Small Business Innovation Research Grant; Sucrose; System; TLR4 gene; Temperature; Testing; Texas; Transgenic Mice; Trehalose; United States Food and Drug Administration; Vaccine Adjuvant; Vaccines; Virus Diseases; aluminum sulfate; antigen binding; base; cold temperature; immunogenicity; mouse model; nanoparticle; neutralizing antibody; next generation; novel vaccines; particle; prevent; receptor binding; reconstitution; social; thermostability; vaccine candidate; vaccine development; vaccine distribution; vaccine platform; viral entry inhibitor

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

项目概要 由严重急性呼吸系统综合症引起的 2019 年冠状病毒病（COVID-19）全球大流行 冠状病毒 2 (SARS-CoV-2) 在我们一生中是前所未有的，已造成重大社会、经济和社会影响。 人类的苦难。全球累计确诊病例 76,858,506 例，死亡 1,711,498 人 WHO 报告截至 2020 年 12 月。FDA 授权的辉瑞（-80 ℃ 储存）和 Moderna（-20 ℃ 储存）疫苗凸显了所需储存温度较低所带来的挑战。 消除新兴疫苗解决方案的冷链要求可以促进分配并提供 节省大量供应链成本。为了克服冷链要求，POP Biotechnologies 提出 研究诱导自发抗原的新型疫苗佐剂平台的冻干策略 颗粒，使用 SARS CoV-2 刺突 (S) 蛋白的受体结合域 (RBD)。我们是其中 首次证明液体形式的 RBD 颗粒可按顺序有效增加 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组氨酸标记抗原 卟啉磷脂 (CoPoP) 和临床佐剂单磷酰脂质 A 和 QS-21。共聚点 脂质体使抗原快速颗粒化，在生物介质中稳定。在本次合作第一阶段 SBIR提案，我们将评估冻干对构象和热稳定性的影响 由此产生的冻干疫苗，通过生化和生物物理测定进行评估，并将评估其功效 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 对下一代颗粒疫苗系统的要求，这对于资源有限的环境可能至关重要。 与德克萨斯生物医学研究所 (TBRI) 合作，开发了 SARS-CoV 转基因小鼠模型 2感染将用于研究冻干RBD颗粒疫苗诱导的热稳定性。 1

项目成果

Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2.

• DOI: 10.3791/63127
• 发表时间: 2021-11-05
• 期刊: Journal of visualized experiments : JoVE
• 作者: Morales Vasquez D;Chiem K;Silvas J;Park JG;Ye C;Martínez-Sobrido L
• 通讯作者: Martínez-Sobrido L

Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice.

• DOI: 10.1126/sciadv.abj1476
• 发表时间: 2021-12-03
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Mabrouk MT;Chiem K;Rujas E;Huang WC;Jahagirdar D;Quinn B;Surendran Nair M;Nissly RH;Cavener VS;Boyle NR;Sornberger TA;Kuchipudi SV;Ortega J;Julien JP;Martinez-Sobrido L;Lovell J
• 通讯作者: Lovell J

Advanced Materials for SARS-CoV-2 Vaccines.

SARS-CoV-2 疫苗的先进材料。

• DOI: 10.1002/adma.202107781
• 发表时间: 2022-03
• 期刊: Advanced materials (Deerfield Beach, Fla.)
• 作者: Mabrouk MT;Huang WC;Martinez-Sobrido L;Lovell JF
• 通讯作者: Lovell JF

Intranasal Immunization with Liposome-Displayed Receptor-Binding Domain Induces Mucosal Immunity and Protection against SARS-CoV-2.

• DOI: 10.3390/pathogens11091035
• 发表时间: 2022-09-12
• 期刊: Pathogens (Basel, Switzerland)

Bioluminescent and Fluorescent Reporter-Expressing Recombinant SARS-CoV-2.

• DOI: 10.1007/978-1-0716-2453-1_18
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)