Mice were immunized either with unadjuvanted seasonal trivalent influenza vaccine (TIV) or TIV formulated with Vaxfectin (R), a cationic lipid-based adjuvant. Increasing doses of Vaxfectin (R) resulted in increased hemagglutination-inhibition or anti-TIV ELISA antibody titers, with up to a 200-fold increase obtained with 900 mu g of Vaxfectin (R). A >= 10-fold dose-sparing effect was demonstrated with Vaxfectin (R) formulations. Vaxfectin (R) preferentially increased IgG2 titers compared to IgG1 titers, resulting in a balanced IgG isotype distribution. Lower doses of Vaxfectin (R) (30 mu g) did not enhance antibody responses, but increased the number of IFN-gamma secreting T-cells by up to 18-fold. The data demonstrate that Vaxfectin (R) enhances Th1 responses with protein-based seasonal influenza vaccine, and suggest that cellular or humoral immune responses may be preferentially induced by modifying the Vaxfectin (R):antigen ratio in the vaccine formulation. (C) 2009 Elsevier Ltd. All rights reserved.