1237. Robust Adjuvant Activity and Dose-sparing Potential of the Novel Semisynthetic Saponin Adjuvant TQL1055 for Seasonal and Pandemic Influenza

Background Vaccination against both seasonal and pandemic influenza requires effective adjuvants to maximize the utility of limited antigen and to enhance immunogenicity in hyporesponsive at-risk populations. First-generation natural saponins are potent immuno-enhancers but are reactogenic and have supply constraints. As part of a NIH-funded project, the novel semisynthetic saponin TQL1055 was evaluated for its potential to augment the immunogenicity of influenza antigens. Figure 1: TQL1055 Enhances the Antibody Response to a Recombinant Antigen Influenza Vaccine (Flublok®) and Exhibits Antigen Dose-Sparing Effects Figure 2: TQL1055 Exhibits Improved Systemic Tolerability Over QS-21. Methods Groups of 10 C57BL/6J mice were immunized subcutaneously (SC) with Flublok® (H3N2 antigen) alone at either a 4.5 mcg or 1.1 mcg dose, or at a 1.1 mcg dose in combination with 10, 30 or 100 mcg TQL1055 on Days 0 and 21. Sera were analyzed at days 0, 21 and 42 by ELISA for H3N2-specific IgG. Body weights were measured serially. Results A 2-dose series of 1.1 mcg Flublok with TQL1055 elicited anti-H3N2 antibodies in all mice. This effect was TQL1055 dose-dependent, with GMTs of 2178 in the 10 mcg group, 13674 in the 30 mcg group and 48959 in the 100 mcg group. The GMT in all TQL1055 groups was higher than the GMT of 176 in the group receiving 4.5 mcg of Flublok alone. Mice receiving TQL1055 gained weight steadily after immunization, compared with a maximum weight loss of >10% in mice receiving 20 mcg of QS-21. Conclusion TQL1055 exhibits robust adjuvant activity for influenza antigens, demonstrating a dose-sparing effect and improved systemic tolerability compared with QS-21. Taken together, these finding support further evaluation of its potential as an adjuvant for influenza vaccines. Disclosures Chloe Buzz, BS, Adjuvance Technologies (Employee) Eric Farris, PhD, Adjuvance Technologies (Employee) Sean R. Bennett, MD PhD, Adjuvance Technologies (Employee) Pat Frenchick, PhD, Adjuvance Technologies (Consultant) Tyler Martin, MD, Adjuvance Technologies (Employee, Shareholder)