In vivo antigen expression by plasmid DNA could provide a potent and cost-effective vaccine platform if its immunogenicity were improved to induce antigen-specific memory T-cell responses. To study these immune responses, we compared naked DNA vaccine with topical DermaVir formulated with the same HIV-1 (Gag) DNA in the mouse model. Topical DermaVir induced HIV-specific effector memory CD8(+) T-cell responses, which were 2.4-fold higher than those elicited by intramuscular injection of naked DNA. DermaVir, but not naked DNA vaccination, induced robust HIV-specific central memory T-cells responses, which are likely to be more efficient in mediating protective immunity. DermaVir formulation combined with topical administration provides an improved immunogenicity of antigen-expressing DNA vaccines.