Thermostabilized Subunit Glycoprotein Vaccine Platform: Immune Characterization of an Emulsified Adjuvant with SARS-CoV-2 Spike Protein and EBOV GP

热稳定亚基糖蛋白疫苗平台：含有 SARS-CoV-2 刺突蛋白和 EBOV GP 的乳化佐剂的免疫表征

• 批准号: 10320057
• 负责人: Oreola Donini
• 金额: $ 82.97万
• 依托单位: SOLIGENIX, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-17 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10320057
• 关键词: 2019-nCoV; Address; Adjuvant; Animal Model; Antibody titer measurement; Antigens; Antiviral Therapy; Attenuated; Awareness; Biological Assay; COVID-19; COVID-19 vaccine; Caregivers; Caring; Cavia; Cells; Cellular Immunity; Cessation of life; Clinical Research; Clinical Trials; Coronavirus; Coupled; Cryopreservation; Democratic Republic of the Congo; Development; Disease; Disease Outbreaks; Disease model; Ebola virus; Elderly; Emergency Situation; Engineering; Environment; Epidemic; Excipients; Family; Family member; Filoviridae Infections; Filovirus; Flow Cytometry; Formulation; Freeze Drying; Funding; Future; GPI-0100; Glycoproteins; Hawaii; Human; Humoral Immunities; Immune; Immune response; Immunity; Immunize; Immunocompromised Host; Immunologic Deficiency Syndromes; Infection; Insecta; Joints; Light; Logistics; Marburgvirus; Mediating; Medical; Medical Staff; Membrane Glycoproteins; Methods; Middle East Respiratory Syndrome Coronavirus; Mus; Particle Size; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Polysorbate 80; Population; Populations at Risk; Pregnant Women; Procedures; Property; Proteins; Public Health; Recombinants; Request for Proposals; Research; Risk; Route; SARS coronavirus; SARS-CoV-2 spike protein; Safety; Structure; Subunit Vaccines; Sudan Ebola virus; Symptoms; System; Testing; Therapeutic; Time; Transformed Cell Line; Universities; Vaccination; Vaccines; Viral; Viral Hemorrhagic Fevers; Viral Vector; Virulence; Virus; Virus Diseases; Work; Zaire Ebola virus; Zika Virus; aluminum sulfate; cell mediated immune response; clinical development; comparative; cost effective; glycosylation; high risk population; immunogenicity; immunosuppressed; improved; medical countermeasure; mortality; mouse model; neutralizing antibody; nonhuman primate; novel; prevent; programs; recombinant virus; response; success; thermostability; vaccine candidate; vaccine development; vaccine formulation; vaccine platform; vector vaccine

7. Project Summary/Abstract The proposal requests funding to support manufacturing and immune characterization of a novel, emulsified adjuvant which is uniquely compatible with lyophilization strategies to enable thermostabilization of glycoprotein vaccines. The major objectives of the study are to transfer and optimize the manufacture of a novel adjuvant and to characterize and assess the comparative immunogenicity of different adjuvant formulations in terms of both humoral and cell mediated immunity, utilizing two different multimeric glycoprotein antigens. Ultimately, this program will identify an optimal adjuvant formulation, capable of potentiating both humoral and cell mediated immunity to protein antigens, compatible with lyophilization and resulting in a thermostabilized vaccine utilizing Generally Regarded as Safe (‘GRAS’) excipients. Specific formulation development will be done in the context of the Zaire ebolavirus (EBOV) GP, a component of our trivalent filovirus vaccine (TriFiloVax) targeting EBOV, Sudan ebolavirus (SUDV) and marburgvirus (MARV) and with SAR-CoV-2 spike protein, supporting COVID-19 vaccine development efforts. While state of the art medical treatment may increase the chances of survival of both the highly fatal EBOV and the highly transmissible COVID-19, currently no antiviral therapy is available to prevent or cure the disease. Vaccination remains the most feasible route for addressing and preventing future epidemics. Ongoing clinical development in the context of EBOV has identified both therapeutics and vaccines which are being tested in the ongoing outbreak in the Democratic Republic of Congo. However, these approaches are highly selective for EBOV only. The sole approved vaccine is a virally vectored vaccine requiring cold storage (<-60°C) storage / distribution and also cannot be used in at-risk populations showing any signs of immunodeficiency or in pregnant women and is potentially more variable in less responsive populations. These vaccine platforms also may not be used repeatedly (either as boosters or with other protein antigens) because of the humoral induced immunity to the viral platform which occurs with vaccination. There is no vaccine for MARV, SUDV or COVID-19. In contrast, subunit vaccines offer many advantages, including improved safety, compatibility with immunosuppressed, immunocompromised or high risk populations or those who have previously received virally vectored vaccines. Thermostabilized formulations also facilitate stockpiling and emergency use in logistically challenging environments. The specific aims of the proposal include to i) transfer manufacturing methods and manufacture engineering lots of CoVaccine with varying Polysorbate 80 content and ii) characterize the enhancement of both humoral and cell mediated immunity by CoVaccine HT™ with SARS-CoV-2 Spike protein and EBOV GP, thereby facilitating the development of TriFiloVax (for EBOV, MARV and SUDV) and CiVax (for COVID-19) and more generally for other protein vaccines.

7.项目总结/摘要 该提案要求提供资金，以支持一种新型乳化 佐剂，其与冻干策略独特地相容，以使 糖蛋白疫苗本研究的主要目的是转移和优化生产的一个 新型佐剂，并表征和评估不同佐剂的比较免疫原性 利用两种不同的多聚体糖蛋白，在体液和细胞介导的免疫方面提供制剂 抗原最终，该计划将确定一种最佳的佐剂配方，能够增强 体液和细胞介导的对蛋白抗原的免疫，与冻干相容， 热稳定的疫苗，其使用通常被认为是安全的（“GRAS”）赋形剂。特定制剂 开发将在扎伊尔埃博拉病毒（EBOV）GP的背景下进行，这是我们的三价疫苗的一个组成部分。 靶向EBOV、苏丹埃博拉病毒（SUDV）和马尔堡病毒（MARV）的丝状病毒疫苗（TriFiloVax）， SAR-CoV-2刺突蛋白，支持COVID-19疫苗开发工作。虽然最先进的医疗技术 治疗可以增加高致命性EBOV和高传播性EBOV的存活机会。 COVID-19，目前没有抗病毒治疗可用于预防或治愈该疾病。接种疫苗仍然是 这是解决和预防未来流行病的最可行途径。正在进行的临床开发 EBOV的背景下，已经确定了正在进行的爆发中测试的治疗方法和疫苗 在刚果民主共和国。然而，这些方法仅对EBOV具有高度选择性。鞋底 批准的疫苗是需要冷藏（<-60 °C）储存/分配的病毒载体疫苗，并且还 不能用于有免疫缺陷迹象的高危人群或孕妇， 可能在反应较低的人群中更易变。这些疫苗平台也可能不会被使用 由于体液诱导的免疫力， 接种疫苗时出现的病毒平台。目前还没有针对MARV、SUDV或COVID-19的疫苗。与此相反， 亚单位疫苗提供了许多优点，包括改进的安全性，与免疫抑制剂的相容性， 免疫功能低下或高危人群或先前接受过病毒载体疫苗的人群。 热稳定配方还有助于储存和在后勤困难的紧急情况下使用 环境.该提案的具体目标包括：i）转让制造方法和制造 具有不同聚山梨酯80含量的CoVaccine工程化批次，和ii）表征 通过具有SARS-CoV-2刺突蛋白和EBOV GP的CoVaccine HT ™的体液和细胞介导的免疫， 从而促进TriFiloVax（用于EBOV、MARV和SUDV）和CiVax（用于COVID-19）的开发， 更普遍地用于其他蛋白质疫苗。