Rational Design of a Broadly protective Live Attenuated Influenza A Vaccine for use in Swine

This project seeks to construct and further develop a broadly protective, tri-valent Swine Influenza (SIV) vaccine that Codagenix will test in collaboration with the USDA-ARS at the National Animal Disease Center under ARS Agreement Log # 57401; (letter from Area Director and CRADA document attached). In proof of concept studies we have demonstrated that our vaccine platform technology was capable of yielding a highly attenuated and efficacious H1N1 influenza vaccine candidate - CodaVax. CodaVax has efficacy in ferrets at an ultra-low dose indicating that SIV vaccines constructed using our technology could be rapidly developed and deployed in the event of an emergency. Furthermore, CodaVax was able to protect mice against lethal challenge using highly pathogenic H5N1 "bird" flu - indicating the cross-protective capability of influenza vaccines designe dusing our platform. In Phase I we will focus on the in vitro construction of field-relevant H1N2 and H3N2 candidate vaccine strains using the same strategy we developed in our pilot H1N1 study. Also in Phase I will test CodaVax in swine in collaboration with USDA-NADC to demonstrate CodaVax efficacy in swine. Our technology, termed Synthetic Attenuated Virus Engineering (SAVE), recodes the viral genome to have a "de-optimized" level of translation of viral proteins in the host cell. This deoptimization is achieved via hundred of genetically stable silent mutations, that retain 100% identity to the wildtype protein sequence. SAVE was first applied to poliovirus (Coleman Science 2008), but has now been validated in seven distinct viral targets including influenza (Mueller Nature Biotech. 2010). SAVE-deoptimized vaccine strains are avirulent while preserving highly immunogenic properties at low doses since they are antigenically identical to the parental wild type strain. The swine industry is >$100B globally and an SIV outbreak has the potential to dramatically reduced the commercial output of this industry by lowering swine weights and leading to mortality. A rapidly deployable, broadly reactive SIV vaccine is needed to safeguard this industry from the clear negative impact SIV could have each season or in an outbreak. This is best accomplished with a live attenuated vaccine.