Enhanced T helper 1 (Th1) responses with Fluzone® adjuvanted with a synthetic TLR4 agonist in an emulsion (45.15)

Impairments in anti-influenza Th1 responses are associated with the significantly greater risk of influenza related mortality in the elderly population. Developing appropriate adjuvants for seasonal influenza vaccines could therefore improve protection against influenza in the elderly. In this study we compare the activity of three different adjuvants, an oil-in-water emulsion and a synthetic lipid A adjuvant formulated with or without an emulsion, to enhance the immunogenicity of the Fluzone influenza vaccine. Fluzone combined with lipid A plus an emulsion was the most effective vaccine tested in mice, which induced greater vaccine-specific IgG2a and IgG titers, enhanced HI titers and the production of Th1-mediated cytokine responses (IFN-γ and IL-2) to each of the Fluzone components. In contrast, while the Fluzone vaccine plus the emulsion induced good antibody responses and HI titers to all of the vaccine components following a boost, a Th2-mediated cytokine response (IL-5) and IL-10 was induced. We demonstrate that in addition to antibody responses, cytokine responses may also be needed for evaluation and characterization of new adjuvants formulations for influenza vaccines. This work was supported in part by Grant #42387 from the Bill & Melinda Gates Foundation