Abstract
BACKGROUND: Current seasonal influenza vaccines elicit sub-optimal immune responses, allowing the virus to continually spread and cause disease from season to season. The inclusion of wild-type vaccine antigens and classical egg-based manufacturing practices often lead to the production of influenza vaccines that are strain specific and not well-matched to actively circulating viruses. METHODS: Computationally optimized broadly reactive antigens (COBRAs) for influenza were expressed as recombinant hemagglutinin (HA) proteins for use as subunit vaccines. These COBRA HA vaccines were adjuvanted with an emulsion system containing synthetic toll-like receptor 4 (TLR4) and TLR7/8 adjuvants, TRAC478 emulsion, or a synthetic saponin adjuvant system (SAS) and were evaluated for their ability to elicit influenza-specific humoral and cellular immune responses in cohorts of influenza naïve mice and pre-immune ferrets. FINDINGS: In the mouse and ferret models, the adjuvanted COBRA H1 and H3 HA vaccine candidates outperformed unadjuvanted HA subunit vaccines by generating higher total IgG and hemagglutination inhibition (HAI) specific antibody titers and elicited a higher frequency of antigen-specific antibody and interferon-gamma (IFN-γ) secreting cells. INTERPRETATION: These results highlight the potential benefits of combining broadly protective vaccine candidates with modern adjuvant systems to increase seasonal influenza vaccine efficacy against antigenically drifted strains of influenza. FUNDING: Funding bodies are described in the Acknowledgements section.