Hantavirus (HTV) DNA vaccine pVAX-LAMP/Gn established memory immune responses. Only pVAX-LAMP/Gn gained long-term seroconversion compared with inactivated vaccine. Enhanced CTL cytotoxicity and Th IFN-γ activity defined cellular memory immunity. Epitope-spreading phenomenon suggested cross-species T-cell hot-spot on Hantaan virus Gn. Safety of pVAX-LAMP/Gn was reconfirmed through behavioral and histological analysis.