DEVELOPMENT OF COVALENTLY BOUND HYALURONIC ACID AS AN ADJUVANT FOR MULTIVALENT LYME DISEASE VACCINE

This project will develop our novel, covalently attached HyA as an adjuvant for use with our multi-immunogen Lyme Disease (LD) vaccine. Our specific aims are as follows: 1) Scale and produce an adjuvanted mosaic8- OspC-mi3 vaccine candidate, 2) Determine optimal configuration of covalent HyA attachment for adjuvanting the LD candidate vaccine, 3) Demonstrate long-term shelf-life and stability of HyA adjuvanted mosaic-8-OspC- mi3 vaccine candidate, 4) Determine optimal adjuvanted dose of mosaic-8-OspC-mi3 vaccine candidate, 5) Demonstrate HyA adjuvanted mosaic-8-OspC-mi3 vaccine candidate is superior for protection against Borrelia infection in mice, and 6) Demonstrate HyA adjuvanted mosaic-8-OspC-mi3 vaccine candidate is superior for protection against tick borne infection in mice. We will use a comprehensive series of side-by-side in vivo comparisons against known, proven, adjuvants (alum and AddaVax) to determine the optimal structural components (size and number of HyA attachments) that provide optimal immunogenicity and protective efficacy against multiple LD challenges both bacterial and tick-based. We will also demonstrate that glycosylation with HyA leads to stability following lyophilization to increase shelf-life facilitate stockpiling. The result of this Phase II deliverable will be a promising, new, self-adjuvanting vaccine candidate for LD suitable for further product development.