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

COVID-19大流行不仅强调了疫苗的重要性，也强调了疫苗佐剂的重要性。迄今为止，植物皂苷已经产生了一些最强大的疫苗佐剂。本项目旨在将商业上可行的高丰度皂苷QS-18与基于钴卟啉-磷脂（CoPoP）的自发纳米脂质体抗原微粒化技术进行联合收割机开发，并已展示其临床应用并进入III期临床试验。流感将被用作模型疾病来研究QS-18的优势。该项目将提供必要的试点数据，以临床翻译为重点的毒性（小鼠和家兔）和有效性（1）制备和获得良好表征的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脂质体组分的浓度;（3）测定CoPoP/QS-18脂质体组分的储存稳定性;（4）测定CoPoP/QS-18脂质体和CoPoP/QS-21脂质体的先导毒性;（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应答;（6）评估CoPoP/QS-18如何在使用小鼠适应的H1、H3和B流感病毒株的小鼠攻击中诱导保护性免疫应答;（7）评估雪貂中对流感病毒攻击的保护。

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.