Type-1 T cell responses and gene signatures driven by a novel virus-like particle (VLP) influenza A (H1N1) vaccine

Effective influenza vaccination is currently assessed by the induction of antibodies directed against the influenza virus envelope glycoprotein hemagglutinin (HA; HAI test) otherwise known as seroconversion. However, protective antibody responses are sub-optimal in some vaccinated populations, particularly in the elderly. Furthermore, many clinical studies highlight the importance of T cells in driving protection. Therefore, a need exists for vaccine strategies which can engage both the humoral and cell mediated arms of the immune response. Herein, we describe the induction of anti-influenza T cell responses following vaccination with a novel VLP vaccine. Peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with either influenza or vaccine specific antigens led to increased CD4 + and CD8 + T cell proliferation and increased production of cytokines such as IL-17A, IL-17F, IL-5, IL-13, IL-9, IL-10, IL-21 and, most significantly, IFN-γ. A subset of individuals demonstrated a shift from a pre-vaccination IL-5- and IL-13- driven type-2 response to a more protective IFN-γ driven type-1 response following vaccination with VLP. Microarray of whole blood samples collected pre- and post-vaccination with VLP revealed significantly different transcriptional profiles. The top most significantly downregulated gene following VLP vaccination, DEAD Box Helicase 17 (DDX17), was also found to have reduced protein expression in PBMCs by flow cytometry. Finally, weighted gene correlation network analysis (WGCNA) revealed that the post vaccination reduction in protein expression of DDX17, increase in HAI titres and increase in T cell proliferation correlates with particular gene modules.