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.

摘要