MULTIVALENT QS-18 PROTEIN NANOPARTICLES FOR A BROADLY PROTECTIVE INFLUENZA VIRUS VACCINE

新冠肺炎疫情突显了不仅疫苗的重要性，还有疫苗佐剂的重要性。到目前为止，植物皂苷已经产生了一些最有效的疫苗佐剂。本项目旨在将商业上可行的高度丰富的皂苷QS-18与基于钴卟啉磷脂(CoPoP)的自发纳米脂质体抗原颗粒化技术相结合，并已证明其临床应用，进入第三阶段临床试验。流感将作为模型疾病来研究QS-18的优势。该项目将通过以下目的为临床翻译提供必要的初步数据：(1)生产和获得具有良好特性的CoPoP/QS-18脂质体，展示流感血凝素(HA)和神经氨酸酶(NA)抗原；(2)表征CoPoP/QS-18脂质体的组成浓度；(3)测定CoPoP/QS-18脂质体各组分的储存稳定性；(4)测定CoPoP/QS-18脂质体和CoPoP/QS-21脂质体的初步毒性；(5)比较CoPoP/QS-18和CoPoP/QS-21在小鼠免疫后诱导抗原特异性抗体和抗原特异性细胞反应方面的差异；(6)评估CoPoP/QS-18如何使用小鼠适应的H1、H3和B型流感病毒株在小鼠攻击中诱导保护性免疫反应；(7)评估对雪貂对流感病毒攻击的保护作用。

The COVID-19 pandemic has underscored the importance of not only vaccines but also vaccine adjuvants. Plant saponins have yielded some of the most powerful vaccine adjuvants to date. This project seeks to combine and develop QS-18, a commercially viable and highly abundant saponin, with spontaneous nanoliposome antigen particlization technology based on cobalt porphyrin-phospholipid (CoPoP), which has demonstrated its clinical application and entered Phase III clinical trials. Influenza will be used as a model disease to study the advantages of QS-18. The project will provide pilot data necessary to clinical translation focused on toxicity (mouse and rabbits) and efficacy (mouse and ferrets) through the following objectives: (1) Produce and procure well-characterized CoPoP/QS-18 liposomes, displaying influenza hemagglutinin (HA) and neuraminidase (NA) antigens; (2) Characterize concentration of components of CoPoP/QS-18 liposomes; (3) Determine storage stability of components of CoPoP/QS-18 liposomes; (4) Determine pilot toxicity of CoPoP/QS-18 liposomes and CoPoP/QS-21 liposomes; (5) Compare CoPoP/QS-18 to CoPoP/QS-21 for inducing antigen-specific antibodies and antigen specific cellular responses following mouse immunization; (6) Assess how CoPoP/QS-18 induces protective immune responses in a mouse challenge using mouse adapted H1, H3, and B influenza virus strains; (7) Assess protection from influenza virus challenge in ferrets.