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 BlueWillows 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.
Public Health Relevance Statement: Project Narrative Respiratory Syncytial Virus (RSV) is a common cause of upper and lower respiratory tract infections and immunocompromised individuals (e.g. infants, young children and elderly) are at particularly high risk of severe infection and disease. There is no FDA-approved vaccine currently available to treat RSV and other therapies have either limited efficacy and/or are plagued by adverse side-effects. In this proposal, we will apply our proprietary NanoVaxTM nanoemulsion adjuvant technology to enable future manufacturing of a potent RSV vaccine that is safe, and facilitates intranasal delivery to confer protective, mucosal immunity against the virus.
Project Terms: Acute; Adjuvant; Adolescence; Adult; African Green Monkey; Age; Agreement; Airway Disease; aluminum sulfate; Animal Model; Animals; Anthrax disease; Antibody titer measurement; Antigens; Asthma; B-Lymphocytes; base; Biological; Blood; Body Weight decreased; Bronchiolitis; Bronchitis; Child; Chronic Obstructive Airway Disease; Clinical; Clinical Trials; cohort; Collaborations; commercialization; Common Cold; Congestive Heart Failure; Cotton Rats; Croup; cytokine; Dependence; design; Development; Disease; Dose; Effectiveness; Elderly; Engineering; Enzyme-Linked Immunosorbent Assay; Evaluation; experience; experimental study; FDA approved; Financial Hardship; flu; Formulation; Foundations; Future; Generations; GMP lots; Health; Healthcare Systems; high risk; Human; Immune; Immune response; Immunization; Immunize; Immunocompromised Host; immunogenic; immunogenicity; Immunoglobulin A; Immunoglobulin G; Individual; Infant; Infection; innovation; innovative technologies; Intramuscular; Intranasal Administration; Lead; Licensing; Lower Respiratory Tract Infection; Lung; manufacturing process; manufacturing scale-up; Measures; Medical; meetings; Methods; Modeling; Molecular Conformation; Monitor; mouse model; Mucosal Immune Responses; Mucosal Immunity; mucosal vaccine; Mucous Membrane; Mus; nanoemulsion; Nasal cavity; neonatal infection; novel; patient population; Phase; Plasmids; Pneumonia; Population; pre-clinical; preclinical safety; preservation; prevent; Procedures; Process; Process Assessment; process optimization; Production; programs; Proteins; Protocols documentation; Quality Control; Recombinants; recurrent infection; Research; respiratory; Respiratory Mucosa; Respiratory syncytial virus; Respiratory Syncytial Virus Infections; Respiratory syncytial virus RSV F proteins; Respiratory Syncytial Virus Vaccines; response; Risk; Safety; scale up; Serum; side effect; Small Business Innovation Research Grant; Spleen; Technology; Testing; Time; Toxic effect; United States National Institutes of Health; Vaccinated; Vaccine Design; vaccine development; Vaccines; Viral; Viral Pathogenesis; Virus; Virus Diseases
