Optimization of vaccine antigen for the development of improved influenza

Optimization of vaccine antigen for the development of improved influenza vaccines ABSTRACT Despite over years of vaccine development influenza remains a persistent global challenge for public health authorities Even with high public awareness and sustained vaccination efforts by health agencies influenza is still estimated to cause greater than annual hospitalizations in the U S with more than deaths On a global scale the WHO estimates that seasonal influenza is responsible for million cases of severe disease and up to deaths each year While heterotypic shifts in influenza A subtypes e g H vs H play a substantial role in this challenge recent studies have shown that even homotypic protection is rapidly lost throughout each influenza season substantially limiting vaccine efficacy The majority of currently licensed influenza vaccines rely on inactivated viral antigens but the method of inactivation is becoming outdated relying on inactivation approaches that are limited to b propiolactone formaldehyde or ultraviolet irradiation However we and others have shown that optimal inactivation is crucial for maintaining key antigenic epitopes and eliciting robust protective immunity and that many common inactivation methods fail to produce optimal vaccines To better address this unmet need we have developed an advanced oxidation based approach to virus inactivation and discovered a unique technique for protecting antigenic epitopes that results in more immunogenic vaccine formulations In particular we have established an approach based on Fenton type oxidation chemistry using optimal concentrations of Cu cupric ion in conjunction with H O hydrogen peroxide Moreover we have identified a novel Cu carrier molecule that not only reduces antigenic damage but also provides more efficient virus inactivation Here we provide preliminary data on this exciting and innovative new platform technology which demonstrates rapid virus inactivation while fully preserving viral HA hemagglutination activity and greatly improved in vivo potency We propose a detailed research plan to expand on this novel approach to influenza inactivation with the ultimate goal of developing improved vaccine formulations able to elicit durable vaccine mediated immunity for the prevention of seasonal influenza PROJECT NARRATIVE Seasonal influenza vaccines suffer from limited efficacy even when the vaccine is well matched to circulating strains In this Phase I SBIR proposal we demonstrate promising preliminary data supporting the use of our advanced oxidation system for the development of improved seasonal influenza vaccines Through this project will develop lead vaccine candidates using a range of rigorous in vitro and in vivo assays with the goal of producing novel influenza vaccine formulations