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

7.项目摘要/摘要 该提案要求提供资金，以支持一种新型乳化剂的制造和免疫表征 唯一与冷冻干燥策略相兼容的佐剂，以实现热稳定 糖蛋白疫苗。这项研究的主要目标是转移和优化制造 新型佐剂及不同佐剂的比较免疫原性鉴定与评价 利用两种不同的多聚体糖蛋白的体液免疫和细胞免疫制剂 抗原。最终，该计划将确定一种最佳佐剂配方，能够增强两者 对蛋白质抗原的体液和细胞免疫，与冷冻干燥相容，并导致 使用通常被认为是安全的(‘GRAS’)辅料的热稳定性疫苗。具体配方 将在扎伊尔埃博拉病毒(EBOV)GP的背景下进行开发，这是我们三价的一个组成部分 针对EBOV、苏丹埃博拉病毒(SUDV)和马尔堡病毒(MARV)的丝状病毒疫苗(TriFiloVax) SARS-CoV-2刺突蛋白，支持新冠肺炎疫苗开发工作。而最先进的医疗技术 治疗可能会增加高度致命的EBOV和高度传染性的EBOV的存活机会 新冠肺炎，目前还没有抗病毒疗法可以预防或治愈这种疾病。疫苗接种仍然是 应对和预防未来流行病的最可行途径。正在进行的临床开发在 EBOV的背景已经确定了正在进行的疫情中正在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 批准的疫苗是一种病毒载体疫苗，需要冷藏(-60℃)储存/分发，还 不能用于出现任何免疫缺陷迹象的高危人群或孕妇和 在反应较弱的人群中，可能会有更大的变数。这些疫苗平台也不能使用 由于体液诱导的对该病毒的免疫力，反复使用(或作为助剂或与其他蛋白质抗原) 接种疫苗时出现的病毒平台。目前还没有针对MARV、SUDV或新冠肺炎的疫苗。相比之下， 亚单位疫苗有许多优点，包括更好的安全性，与免疫抑制的兼容性， 免疫受损或高危人群或以前接种过病毒载体疫苗的人群。 热稳定配方还便于储存和在后勤挑战中的紧急使用 环境。该提案的具体目标包括：一)转让制造方法和制造 不同多山梨酸酯80含量的工程疫苗和II)增强的特性 SARS冠状病毒S蛋白与EB病毒gP联合疫苗HT™的体液免疫和细胞免疫 从而促进了TriFiloVax(用于EBOV、MARV和SUDV)和CiVAX(用于新冠肺炎)的开发 更广泛地说，用于其他蛋白质疫苗。

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.