A Novel TLR Agonist Based Adjuvant for Poliovirus Vaccine

PROJECT SUMMARY ABSTRACT Antiviral vaccines remain the largest segment of the rapidly growing global vaccine market Despite near complete eradication of poliovirus through vaccination efforts continued need for inactivated polio vaccine IPV is projected to reach million doses per year worldwide Among major obstacles to widespread use of the current IPV formulation are its high cost and insufficient potency to induce robust intestinal immunity Therefore development of an effective safe and affordable adjuvant for IPV that would allow reduction of the costly IPV antigen content represents a highly significant unmet need This Phase I SBIR proposal aims to address this challenge through optimization of a novel adjuvant system combining the immunostimulatory power of the toll like receptor TLR agonist entolimod previously CBLB with the well known adjuvant properties of Alum Entolimod is being developed for tissue protective anti radiation and supportive care in cancer treatment and anticancer immunotherapeutic applications by Cleveland BioLabs Inc CBLI and has an established safety profile Given the demonstrated adjuvant properties of the natural TLR agonist and entolimod parent flagellin investigators of this proposal in partnership with CBLI developed an innovative entolimod Alum based adjuvant system termed SA with advantages in terms of efficacy combined effect of two adjuvants versatility modular platform easily customized for many different antigen types and decreased futile adjuvant directed immunogenicity Preliminary studies confirmed that immunization of mice with IPV human dose co adsorbed on SA led to induction of increased levels of anti poliovirus neutralizing antibodies compared to immunization with IPV alone or IPV Alum Here we propose further optimization of entolimod as a co adjuvant through targeting of its residual immunogenicity and its ancillary inflammasome directed signaling activity Aim followed by characterization and optimization of the stability efficacy and safety of SA IPV formulations containing the identified optimal entolimod variant Aim In addition we will determine the impact of entolimodandapos s residual immunogenicity on adjuvant activity of SA via mapping and elimination of mouse T cell epitopes Together the deliverables of these aims will define and validate an optimal design for the SA platform and a new SA IPV formulation and set the stage for Phase II SBIR application and commercialization Project Narrative The proposed development of a novel modular and versatile adjuvant system combining a rationally optimized agonist of the TLR innate immunity receptor with Alum will address a significant medical need for potent safe and affordable poliovirus vaccine formulation and open additional opportunities on the rapidly growing global vaccine market