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，而且还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。该项目旨在结合和开发QS-18，这是一种商业上可行且高度丰富的皂苷，以及基于钴卟啉磷脂（COPOP）的自发纳米脂质体抗原颗粒化技术（COPOP），已证明其临床应用并进入了III期临床试验。流感将被用作模型疾病，以研究QS-18的优势。该项目将通过以下目标提供针对毒性（小鼠和兔子）和功效（小鼠和雪貂）的临床翻译所必需的试验数据：（1）产生和购买良好的copop/QS-18脂质体，显示流感的甲状腺素（HA）和Neuraminidase（NA）抗原酶抗原型甲状腺素（HA）和Neuraminidase; （2）表征Copop/QS-18脂质体的成分浓度； （3）确定Copop/QS-18脂质体组件的存储稳定性； （4）确定Copop/QS-18脂质体和Copop/QS-21脂质体的试验毒性； （5）将Copop/QS-18与Copop/QS-21进行比较，以诱导小鼠免疫后诱导抗原特异性抗体和抗原特异性细胞反应； （6）评估使用小鼠改编的H1，H3和B流感病毒菌株的Copop/QS-18如何在小鼠挑战中诱导保护性免疫反应； （7）评估在雪貂中侵害流感病毒挑战的保护。