DNA vaccination with microneedles (MNs) into the skin represents a potential therapeutic approach for the clinical treatment of viral diseases as well as for intradermal genetic immunization. In this study, we investigated a DNA vaccination against the severe fever with thrombocytopenia syndrome virus (SFTSV) delivered by nano-patterned microneedtes (nMNs) to improve the efficiency compared to a conventional MN vaccination. Because DNA vaccinations delivered by coated MNs have major disadvantages such as a poor coating efficiency and immunogenicity, additional excipients are necessary. Therefore, we developed nMNs to improve the affinity of stainless steel for plasmid DNA vaccinations. The results show that the nMNs have an improved DNA vaccine loading capacity because their surfaces have an increased hydrophilicity from the high surface/volume ratio. The cytocompatibility analysis also showed a higher cell proliferation when using the nMNs. Finally, the in vivo experiments with balb/c mice vaccinated with the SFTSV DNA vaccine-coated nMNs generated a higher level of cellular immune responses than that of the unmodified MNs. (C) 2017 Elsevier B.V. All rights reserved.