Pre-clinical testing of T cell responses to influenza vaccine/adjuvant combinations in older adults (132.5)

Abstract

Abstract Objective: The purpose of this experiment was to determine whether inflammatory cytokines or TLR ligands could be combined with influenza vaccine in older adult PBMC to enhance the response to live influenza virus challenge. Methods: PBMC from five older adults (>65 years old) and six young (20-38 years old) adults were obtained at six months post-vaccination and cultured for five days with split-virus vaccine (SVV) and the TLR3 ligand, poly I:C, or a cocktail of pro-inflammatory cytokines (TNF-α, IL-1, IL-6; T/1/6). Stimulated PBMC were then challenged with live influenza virus for 20 hours and supernatants and lysates prepared for assays of IL-1, IL-6, TNF-α in 5-day supernatants, and the IFN-γ:IL-10 ratio and granzyme B activity in 20-hour virus-challenged PBMC. Results: We observed an increased response to SVV in younger compared to older adults, but a dose-response relationship between poly I:C (added to a fixed dose of SVV) and the IFN-γ:IL-10 ratio and granzyme B levels improved the response in older adult PBMC. This response was associated with a dose-response increase in pro-inflammatory cytokine levels in SVV/poly I:C-stimulated PBMC. However, a cocktail of these inflammatory cytokines (T/1/6) added to the PBMC culture suppressed rather than enhanced the T cell response in older adults. Conclusion: Poly I:C combined with influenza vaccine was shown to enhance the T cell response to influenza in aged PBMC by mechanisms that cannot be replicated by the simple addition of inflammatory cytokines to the vaccine.