Development of an improved intranasal vaccine against influenza

Despite the development of several types of influenza vaccines (live-attenuated, inactivated, subunit), the World Health Organization estimates that seasonal influenza is still responsible for 3-5 million cases of severe disease and 290,000-650,000 deaths each year. Although vaccination programs have helped to reduce the morbidity and mortality associated with seasonal influenza, current vaccine approaches are limited by poor vaccine- mediated immunity and low vaccination coverage. To overcome suboptimal immune responses to influenza vaccination, we have developed an advanced hydrogen peroxide-based, site-directed oxidation technology that renders viruses fully inactivated while preserving protective structures/epitopes on the virus surface including fully maintained HA (hemagglutinin) activity. Our preliminary data shows that immunization of mice with our 1st- generation peroxide-inactivated vaccine by either the subcutaneous, transcutaneous, or intranasal routes of administration leads to full protection against lethal influenza challenge. In these proposed studies, we describe our 2nd-generation HydroVax platform technology and the approaches that we will take to further optimize vaccine potency following intranasal vaccination. By improving the structural integrity of the vaccine antigen, coupled with the ease and acceptability of an intranasal route of administration, we hope to improve both vaccine potency and vaccination coverage that together, will greatly reduce the impact of seasonal influenza among vulnerable populations including infants and the elderly.In this proposal, we provide exciting preliminary data describing an advanced HydroVax vaccine platform that will be used to develop a novel peroxide-inactivated influenza virus vaccine optimized for effective intranasal vaccination.