A Novel and More Effective Bivalent Live-attenuated Influenza Vaccine

Research Objectives: The overall goal of this application is to generate, for the first time, a novel and more effective LAIV for the prevention and control of EIV in the horse population based on reverse genetics approaches. This is a highly innovative proposal aimed to provide, for the first time, an intranasal competitive cold-adaptive, temperature sensitive LAIV based on reverse genetic approaches for the prevention and treatment of EIV in horses (4-6). To that end, we will combine our currently available state-of-the-art plasmid-based reverse genetic approaches (9-12) with modifications in th~ viral PB2 and PB 1 polymerase subunits (13, 14) of influenza A/equine/Ohio/1/2003 H3N8 to make a cold-adapted, temperature sensitive clade 1 LAIV (15, 16). Then, using the safety backbone of our A/equine/Ohio/1/2003 H3N8 clade 1 as a master donor virus (MDV) (12, 13, 17), we will generate a clade 2 A/equine/Richmmond/1/2007 LAIV. Both clade 1 A/equine/Ohio/1/2003 H3N8 and clade 2 A/equine/Richmmond/1/2007 LAIV will be used in a blended bivalent LAIV for the treatment of EIV. Our LAIV bivalent approach should be more effective than current inactivated EIV vaccines because of the better immunogenic protective properties associated with LAIV. Moreover, it will be more effective than the currently available LAIV (8) to treat EIV infections in horses because of strain match with currently circulating EIV strains (6). Importantly, and contrary to the current EIV LAIV, our LAIV could be updated at any given time to adapt to newly circulating or potentially pandemic EIV strains with the final purpose being the prevention and control of equine influenza in horses.