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

用于广泛保护性流感病毒疫苗的多价 QS-18 蛋白纳米颗粒

• 批准号: 10933284
• 负责人: KENTNER SINGLETON
• 金额: $ 59.98万
• 依托单位: POP BIOTECHNOLOGIES, INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2025-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10933284
• 关键词: Adjuvant; Antibodies; Antigens; Austria; COVID-19 pandemic; Cobalt; Contractor; Data; Disease model; Ferrets; Immune response; Immunization; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B Virus; Influenza Hemagglutinin; Liposomes; Mus; Neuraminidase; Oryctolagus cuniculus; Phase III Clinical Trials; Phospholipids; Plants; Porphyrins; Proteins; QS21; Quillaja; Saponins; Soapbush; Soaps; Technology; Toxic effect; Toxicology; Tree Bark; Vaccine Adjuvant; Vaccines; clinical application; clinical translation; influenza virus strain; influenza virus vaccine; influenzavirus; nanoliposome; nanoparticle; response; trivalent influenza vaccine

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.

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。本项目拟将具有商业可行性、丰度高的皂苷类化合物q -18与基于卟啉-磷脂钴（CoPoP）的纳米脂质体自发抗原颗粒化技术结合开发，并已完成临床应用并进入三期临床试验。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标为临床翻译提供必要的试点数据，重点关注毒性（小鼠和兔子）和有效性（小鼠和雪貂）：(1)生产和采购具有良好特征的CoPoP/ qc -18脂质体，显示流感血凝素（HA）和神经氨酸酶（NA）抗原；(2)表征CoPoP/QS-18脂质体组分浓度；(3)测定CoPoP/QS-18脂质体组分的贮存稳定性；(4)测定CoPoP/QS-18脂质体和CoPoP/QS-21脂质体的中试毒性；(5)比较CoPoP/QS-18与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的效果；(6)评估CoPoP/QS-18如何在使用小鼠适应的H1、H3和B型流感病毒株的小鼠攻击中诱导保护性免疫反应；(7)评估对雪貂流感病毒攻击的保护作用。