Development of a Mucosal Nanoemulsion-Adjuvanted RSV Vaccine using Recombinant Pre-Fusion F Protein

使用重组预融合 F 蛋白开发粘膜纳米乳佐剂 RSV 疫苗

• 批准号: 10510895
• 负责人: Shyamala Ganesan
• 金额: $ 85.35万
• 依托单位: BLUEWILLOW BIOLOGICS, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10510895
• 关键词: Acute; Address; Adjuvant; Adolescence; Adult; Age; Agreement; Airway Disease; Antigens; Asthma; Biological Assay; Biological Products; Bronchiolitis; Bronchitis; Cell Line; Cessation of life; Child; Childhood; Chronic Obstructive Pulmonary Disease; Clinical Trials; Coenzyme A; Common Cold; Congestive Heart Failure; Cotton Rats; Croup; Cyclic GMP; Development; Disease; Effectiveness; Elderly; Exhibits; FDA approved; Financial Hardship; Formulation; Foundations; Future; Health; Healthcare Systems; Hospitals; Human; Immune response; Immunization; Immunocompromised Host; Individual; Infant; Infection; International; Intramuscular; Lead; Licensing; Lower Respiratory Tract Infection; Lung; Medical; Molecular Conformation; Mucosal Immune Responses; Mucosal Immunity; Mucous Membrane; Patient-Focused Outcomes; Phase; Pneumonia; Population; Process; Production; Proteins; Recombinants; Research; Respiratory Mucosa; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory syncytial virus; Respiratory syncytial virus RSV F proteins; Risk; Route; Running; Seeds; Sexual Transmission; Ships; Small Business Innovation Research Grant; Technology; Technology Transfer; Therapeutic; United States; United States National Institutes of Health; Vaccination; Vaccine Design; Vaccines; Vial device; Viral; Viral Antigens; Viral Pathogenesis; Virus; Virus Diseases; Visit; Work; cell bank; clinical development; clinical material; cost; high risk; immunogenicity; improved; infant infection; innovation; manufacturing process; mortality; nanoemulsion; novel; pathogen; preservation; prevent; protein expression; recurrent infection; respiratory; side effect; success; vaccine access

ABSTRACT Respiratory syncytial virus (RSV) is extremely ubiquitous, with almost all humans acquiring the infection by the age of two. It is manifested by several secondary acute respiratory illnesses including bronchiolitis croup, bronchitis, pneumonia and the common cold. RSV does not elicit a protective immune response in humans, which results in recurrent infections in children and adults. Infants infected with RSV have a high risk of developing reactive airway disease, such as asthma, through adolescence. RSV pathogenesis in adults can lead to serious complications, including pneumonia, chronic obstructive pulmonary disease, congestive heart failure and asthma. The elderly population is at particularly high risk. These illnesses caused by RSV infection combine to represent a massive worldwide health risk and substantial financial burden to the global healthcare system. There is currently no approved vaccine available to prevent RSV infection or disease. In this SBIR Phase I proposal, BlueWillow Biologics will manufacture the cGMP seeds for producing the recombinant F-protein RSV subunit with a preserved pre-fusion conformation (PrFFP), which would enable future manufacturing of clinical material for intranasal PrFFP/NE01 vaccine. The innovative feature is the application of BlueWillow’s NanoVaxTM nanoemulsion mucosal adjuvant and delivery technology to formulate PrFFP as an intranasal vaccine. This new strategy will activate both systemic and mucosal immunity, a key protective immune response necessary to prevent viral entry and infection locally at the respiratory mucosa including the lungs. Previous RSV vaccines currently under development using F-protein antigens have been formulated for intramuscular delivery, which does not promote mucosal immunity and may compromise their effectiveness against RSV. Successful completion of this SBIR phase 1 proposal will provide the foundation for the clinical development and commercial release of the first mucosal NE-RSV vaccine on the market. We will execute the license agreement with NIH-VRC to obtain cGMP seeds of CHO-DG44 seeds for PrFFP production. Following which we will perform technology transfer from NIH-VRC to BlueWillow and master cell bank for future manufacturing will be established at CDMO. The novel combination of highly antigenic F protein in its pre-fusion conformation with our innovative NanoVaxTM nanoemulsion mucosal adjuvant technology will result in a safe and effective intranasal vaccine to prevent RSV infection and disease in the elderly. This commercial product will fulfill an enormous unmet medical need.

抽象的 呼吸综合病毒（RSV）非常普遍，几乎所有人类都会在两岁的年龄中获得感染。它由几种继发性急性呼吸道疾病（包括支气管炎俱乐部，支气管，肺炎和普通感冒）所表现出来。 RSV不会引起人类受保护的免疫响应，这会导致儿童和成人的复发感染。感染了RSV的婴儿通过青少年患有哮喘等反应性气道疾病的风险很高。成人的RSV发病机理可导致严重的并发症，包括肺炎，慢性阻塞性肺部疾病，充血性心力衰竭和哮喘。老年人的风险特别高。 RSV感染引起的这些疾病共同代表了全球医疗保健系统的巨大全球健康风险和大量财务燃烧。目前尚无批准的疫苗可预防RSV感染或疾病。 在SBIR I期提案中，BlueWillow Biologics将生产CGMP种子，用于生产具有保留的预融合构象（PRFFP）的重组F蛋白RSV亚基（PRFFP），这将使未来的临床材料用于内鼻内PRFFFP/NE01疫苗。创新的特征是Bluewillow的Nanovaxtm纳米乳液粘膜调节和输送技术的应用，以将PRFFFF作为鼻内疫苗。这种新策略将激活全身和粘膜免疫学，这是一种在包括肺在内的呼吸道粘膜下在呼吸道粘膜下进行病毒入口和局部感染所必需的关键保护免疫响应。目前使用F蛋白抗原开发的先前正在开发的RSV疫苗已被制定用于肌内递送，该疫苗不会促进粘膜免疫学，并可能损害其针对RSV的有效性。 该SBIR 1阶段提案的成功完成将为市场上第一种粘膜NE-RSV疫苗的临床开发和商业发布奠定基础。我们将与NIH-VRC执行许可协议，以获取用于PRFFP生产的CHO-DG44种子的CGMP种子。随后，我们将在CDMO中建立从NIH-VRC到Bluewillow和Master Cell Bank的技术转移，以便将来制造。高度抗原F蛋白与我们创新的Nanovaxtm纳米乳胶粘膜调节技术的新型组合将导致安全有效的鼻内疫苗，以防止老年人的RSV感染和疾病。该商业产品将满足巨大的未满足医疗需求。