Tattoo guns use high-frequency oscillating needles to make thousands of punctures in the skin, which is conventionally used to deposit tattoo ink in the dermis, but has been adapted to deliver ID vaccines (Fig. 1d) . In one study, hemagglutininexpressing DNA vaccine was administered to pigs and derived humoral and protective immunity as shown by methods including HAI titer and improved virus clearance from nasal swabbing (Eriksson et al. 1998) . To overcome the slow processing of an immune response induced by DNA vaccination, DNA tattooing was suggested for short-interval DNA vaccination (Bins et al. 2005) . In this study, it was shown that short-interval ID DNA tattoo immunization generated fast and stable T cell responses to human papillomavirus and complete protection from influenza virus challenge. When compared to the IM route, DNA tattoo vaccination elicited much stronger and quicker humoral and cellular immune responses. In addition, studies indicated that even IM immunization with adjuvant was inferior to DNA tattoo immunization (Pokorna et al. 2009 ). To determine the effect of the tattooing process on DNA vaccine stability, the DNA topology change was evaluated, including critical factors for antigen expression and immune response (Quaak et al. 2009 ). It was found that the DNA tattooing tool had negligible effect on DNA structure and activity. Other vaccines including an adenoviral vector vaccine against respiratory syncytial virus (Potthoff et al. 2009 ) and a peptide vaccine against human papillomavirus (Pokorna et al. 2009 ) were administrated by ID tattooing. In the case of the adenoviral vector vaccine, tattooing showed similar performance to ID injection. Tattooing of the peptide vaccine with CpG motifs adjuvant showed better response than IM vaccination with adjuvant.