Pre-existing T cell immune response specific to computationally optimized broadly reactive hemagglutinin antigens (COBRA-HA) in influenza vaccinees

Abstract The biggest challenge in developing a universal influenza vaccine is the extensive antigenic drift. In contrast to humoral immunity, cell-mediated immunity more cross-reactive and can protect against various subtypes drift variants. Our research group has described computationally optimized broadly reactive antigens (COBRA) develop HA-based protective vaccine. However, studies that characterize potential of COBRA-HA elicit functional T-cell response have yet be developed. Cross-reactive conserved T cell epitopes from previous exposure provide an efficient heterologous immunity. Thus, we aim immune profile pre-existing at functionality epitope conservation level identify targets included flu design. To achieve this goal, 50 donors who received seasonal (Fluzone, Sanofi) for two consecutive seasons were HLA typed, candidates Y2 (H1) NG2 (H3) predicted using IEDB software. Using high dimensional flow cytometry, eight peptides 15 combined pools determine phenotypes cytokine secretion. We found vaccination induced COBRA HA-specific CD4+ CD8+ independent antibody titers. Next, will evaluate Th helper subsets (Th1/Th2/Th17/cTfh) breadth by deconvoluting IFNγ Fluospot assay. Nonetheless, next generation recalled response, demonstrating efficacy clinical trials. National Institute Allergy Infectious Diseases (NIAID), U.S. Institutes Health (NIH), Department Human Services contract 75N93019C00052 (TMR).