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Principal Investigator: BRUXANNE EL-KAMMASH
Organization: UNIVERSITY OF CHICAGO
Fiscal Year: 2024
Award: $3,691,826
Funding agency: National Institute of Allergy and Infectious Diseases
Vaccines are formulated with adjuvants to stimulate the immune system so that the vaccine can be more effective at preventing disease. Our goal is to create an adjuvant formulation that overcomes a limitation in many adjuvants - customization of the immune response for a desired immunological outcome. Specifically, our goal is to reduce inflammation and side effects and to increase antibody levels in vaccines used for influenza. In our previous Adjuvant Discovery Contract, we discovered that when a molecule called Bafetinib was combined with a commercial vaccine or traditional adjuvant, Bafetinib can increase antibody titers or lower inflammation, or both. This new contract with the NIAID is an opportunity to improve Bafetinib’s formulation and yield a better adjuvant. We will partner with Inimmune Corporation to combine our molecule, Bafetinib, with their molecule, INI-4001. INI-4001 is promising due to its strong stimulatory properties, readily altered chemical structure, and because Inimmune has extensive expertise in adjuvant development. Together, we will develop an adjuvant system composed of Bafetinib and INI-4001. We will develop Bafetinib in combination with INI-4001 (a synthetic TLR7/8 agonist) through co-formulation or as a stand-alone adjuvant additive. Using targeted synthetic modifications of Bafetinib, we will improve the formulation, molecular composition, stability, and activity in previously vetted vaccine models. Our expected outcomes include optimized formulations of new molecular compositions of the parent structure of Bafetinib with INI-4001 in new formulations we refer to as “adjuvant systems.” These adjuvant systems will use both liposome and oil-in-water emulsion to localize the components. We will compare the performance of our new system to several existing vaccine platforms. We will iterate the formulations and improve them based on results from repeating the performance and toxicity tests. The purpose is to optimize the most promising formulation to develop a final lead candidate. We will test the lead candidate in Ferret challenge models of influenza. We will also test how well the lead candidate can be produced on a larger scale. This knowledge will improve the translation of our research from the small-scale laboratory to production-scale using standard Good Manufacturing Practices.
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