The CpG motifs of bacterial-derived plasmids augment antigen-specific immune responses and steer those responses towards the T helper 1 (Th1) type. In this study, we have addressed the immuno-stimulatory effect of intramuscular co-administration of CpG motifs containing vector DNA on the modulation of immune responses to the haemagglutinin (HA) and the nucleoprotein (NP) proteins of influenza virus. The co-administration of vector DNA with a HA-encoding plasmid DNA showed a significant enhancement in the total IgG response, the generation of cytotoxic T lymphocyte (CTL), and the T-cell proliferative response. In the case of NP-encoding plasmid DNA inoculations, the co-administration of vector DNA slightly decreased the total IgG response, although the IgG2a/IgG1 ratio and the CTL responses to NP were significantly increased. These observations suggest that the immuno-stimulatory effects of bacterial-derived plasmids depend upon the nature of the co-administered antigen.