Ultra-low dose Influenza vaccines

DESCRIPTION provided by applicant Current seasonal Influenza vaccines are proving to be ineffective especially in at risk populations For example this yearandapos s inactivated flu vaccine had only a efficacy rate against H N infections in the elderly and the current live attenuated Influenza vaccine LAIV is aged restricted for those above years of age Therefore there is glaring unmet need seasonal Influenza vaccines that are effective A translational vaccine platform technology developed at Stony Brook University entitled SAVE Synthetic Attenuated Virus Engineering has shown initial success in yielding an anti Influenza A vaccine in the laboratory strain A Puerto Rico that is effective in animals at very low doses This SHIFT award seeks to transform this academic discovery into the beginnings of commercial product by applying the SAVE technology to seasonally relevant human strains and then compare efficacy against the current LAIV Demonstration of superiority will increase the commercial viability of the technology as well as fulfill a current unmet medical need flu vaccines that have high efficacy in all populations The drawbacks of current flu vaccines are two fold both the inactivated injectable vaccine or the current LAIV require a large quantity o viral particles per dose andgt and both have low efficacy in the aged population The SAVE technology could provide a solution to both of these limitations The SAVE platform relies on synthetic biology and the andquot re designingandquot of a target virusandapos s entire genome to yield a vaccine strain This customization process uses software based algorithms to andapos re codeandapos the genome of a target virus Genomic andapos re codingandapos results in a virus that is antigenically identical i e looks exctly like the wild type virulent strain but possesses a genome with hundreds of mutations rendering it attenuated in the host Since proteins of the SAVE designed vaccine strain are one hundred percent identical to the virulent strain animals vaccinated with SAVE designed vaccines develop a robust and protective immune response SAVE is a platform technology that has had preliminary success constructing vaccine candidates for multiple unrelated target viruses including poliovirus and Influenza a virus Science Nature Biotech In Phase I of this proposal we will apply the SAVE technology to construct vaccine candidates for seasonal influenza strains that are clinically relevant and subsequently we will compare these strains to the current commercial live attenuated influenza vaccine to demonstrate commercial viability In Phase II we will build upon our success and test our SAVE designed seasonal influenza vaccine candidates in a ferret model PUBLIC HEALTH RELEVANCE We have developed Influenza vaccine model strains that are highly efficient in experimental animals and work at extremely low doses Due to this low dose requirement our vaccine technology could overcome a critical bottleneck in the influenza vaccine manufacturing process the inadequate availability of sufficient vaccine doses in times of highest vaccine demands such as during a pandemic