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 Fast-Track proposal, BlueWillow Biologics will develop and demonstrate proof-of-concept in pre-clinical animal models, for an effective nanoemulsion-adjuvanted mucosal vaccine against RSV. The nanoemulsion-based vaccine will combine two innovative technologies: 1) The first feature is the use of a highly antigenic recombinant F-protein RSV subunit with a preserved pre-fusion conformation (PrFFP) designed by the NIH; and, 2) The second 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. The Phase I SBIR program will establish compatibility and short-term stability of the PrFFP-NE01 vaccine formulation; demonstrate activation of systemic and mucosal immunity in a mouse model; and demonstrate proof-of-concept for full protection against RSV in the cotton rat challenge model. In SBIR Phase II, BlueWillow will establish and optimize processes for scale up manufacturing for the PrFFP-NE01 mucosal vaccine with engineering scale of 200L; and, assess the immune-protective dose range in adult African Green Monkey models for protection against RSV challenge. Successful completion of this SBIR project will provide the foundation for progression to GMP manufacturing, pre-IND meeting with the FDA, GLP safety-toxicity study, IND filing and clinical trials to assess the PrFFP-NE01 vaccine in the elderly population. 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.
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 formulate a potent RSV vaccine that is safe, and facilitates intranasal delivery to confer protective, mucosal immunity against the virus.
