IMMvention Therapeutix, Inc. — Department of Health and Human Services STTR Phase I: NIAID

Description

Summary Influenza virusa member of the orthomyxovirus familyhas three different types that infect humansABand CTypes A and B produce annual epidemicsand type A influenzawhich resides asymptomatically in birdscan cause pandemic infections in humansIn addition to common flu like symptomse gfeverchillsmalaisemuscle painin susceptible populations influenza can induce potentially fatal secondary complications including bronchitispneumoniaand acute respiratory distressWorldwideinfluenza infection can cause up tomillion severe cases anddeaths per yearInfluenza is also a considerable economic burden with an estimated annual cost of $billion in the U SaloneExisting antivirals can treat influenza but must be given withinhours of infection to be effectiveAdditionallymany flu strains have developed complete resistance to older antiviralsThereforethe best method to dampen the spread of disease is preventative vaccinationEven though traditional influenza vaccines have been on the market since thesthey have several limitationsdependence on egg based technology to grow the viruslimited worldwide vaccine availabilitydecreased efficacy in the elderlyand lack of cross reactivity with various influenza strainsEach yearbased on predictions from the WHO and CDC recommendationsmanufacturers formulate the flu vaccine using just three to four killed or attenuated virusesSincethe influenza vaccine has beeneffective on average with some years showing very low effectiveness of onlyThis poor effectiveness is likely due to the targeted viral strains undergoing antigenic drift and or shiftDevelopment of auniversal flu vaccineusing safe recombinanti enot egg basedsubunit antigens could potentially help overcome the drawbacks of the current influenza vaccine strategyIn order to develop a universal vaccine the immune system must generate a response against conserved epitopes that are found on many different strains of influenzaThese epitopes include the stalk domain of HAthe matrix proteinectodomainand other proteins that induce CDT cell activity against the virusIn order to generate an effective immune response against these subunit antigensan adjuvant must be coadministered to provide protectionWe have preliminary data demonstrating that a novel adjuvant encapsulated in a proprietary microparticleMPcan induce a T helpercellular immune responseand using a universal influenza antigen it can help to provide superior protection against a lethal challenge compared to other commercially available adjuvantsas well as cross reactive antibodies across different viral subtypesBased on this preliminary data we propose scaling up the fabrication of these MPsThe data collected from this proposal would allow us to manufacture these MPs on an industrial scaleWe will validate that the MP adjuvanted subunit antigen can protect against influenza infection and generate an immune response similar to what was fabricated in the bench top settingWe will also study the sterilization of these MPswhich is an important step in the potential manufacturing of the proposed MP platformThe data generated in this proposal will be crucial for a Phase II application Narrative Each year the yearly flu shot can become ineffective due to mutations in the influenza virusBy using proteins that are more conserved between different strains of influenza a universal flu vaccine can be generatedBecause these proteins are not terribly immunogenicwe propose the incorporation of a novel antigen in a biopolymer microparticle !