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

项目摘要 严重急性呼吸系统综合征引起的冠状病毒疾病2019（COVID-19）全球大流行 冠状病毒2（SARS-COV-2）在我们的一生中是前所未有的，并导致了主要的社会，经济和 人类的痛苦。在全球范围内，已经有76,858,506例确认案件，导致1,711,498例死亡 WHO持续到2020年12月。 ModernA（-20°C储存）疫苗强调了较低必需的存储温度所带来的挑战。 消除新兴疫苗解决方案的冷链要求可以促进分配并提供 大量供应链成本节省。为了克服冷链要求，流行生物技术建议 调查其新型疫苗调节平台的冻干策略，该平台可诱导赞助抗原 颗粒，使用SARS COV-2尖峰（S）蛋白的受体结合结构域（RBD）。我们是 首先证明RBD颗粒的液体形式可能会通过订单增加SARS-COV-2中和抗体 与固体抗原相比，数量级。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进行简单混合来表征他标记的抗原 卟啉 - 磷脂（COPOP）和临床调节器单磷酸脂质A和QS-21。 Copop 脂质体引起生物学培养基中稳定的快速抗原颗粒化。在这个协作阶段的第一阶段 SBIR提案，我们将评估冻干对构象和热稳定性的影响 通过生化和生物物理测定评估的冻干疫苗，将评估其有效性 通过小鼠的功能免疫原性。该项目将评估打破冷链的可行性 下一代粒子疫苗系统的要求，这对于资源有限的设置至关重要。 与德克萨斯生物医学研究所（TBRI）合作，这是一种用于SARS-COV-的转基因小鼠模型 2感染将用于研究由冻干的RBD颗粒疫苗引起的保护的热稳定性。 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

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

Systematic comparison between BNT162b2 and CoronaVac in the seroprotection against SARS-CoV-2 Alpha, Beta, Gamma, and Delta variants.

• DOI: 10.1016/j.jinf.2022.02.030
• 发表时间: 2022-05
• 期刊: The Journal of infection
• 作者: Au WY;Ye C;Briner SL;Suarez GD;Han J;Xu X;Park JG;Brindley MA;Martinez-Sobrido L;Cheung PP
• 通讯作者: Cheung PP

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

SARS-CoV-2 Protein Nanoparticle Vaccines Formed In Situ From Lyophilized Lipids.

由冻干脂质原位形成的 SARS-CoV-2 蛋白纳米颗粒疫苗。

• DOI: 10.1002/smll.202304534
• 发表时间: 2024
• 期刊: Small (Weinheim an der Bergstrasse, Germany)
• 作者: Jiao,Yang;Huang,Wei-Chiao;Chiem,Kevin;Song,Yiting;Sun,Jingyu;Chothe,ShubhadaK;Zhou,Shiqi;Luo,Yuan;Mabrouk,MoustafaT;Ortega,Joaquin;Kuchipudi,SureshV;Martinez-Sobrido,Luis;Lovell,JonathanF
• 通讯作者: Lovell,JonathanF