Improved efficacy of an influenza DNA vaccine through high-density microarray patch delivery

Pandemic preparedness requires vaccine platforms that are fast to produce, thermostable and suitable for broad deployment. DNA vaccines are well suited to this task but have historically suffered from poor immunogenicity when delivered by conventional intramuscular (IM) injection. Here, we evaluated high-density microarray patch (HD-MAP) delivery of a DNA vaccine encoding the influenza A/California/01/2009 (H1N1pdm09) haemagglutinin (HA) antigen. <i>In vivo</i> imaging of a luciferase reporter construct demonstrated earlier and higher expression following HD-MAP application compared to IM injection. HD-MAP delivery of the HA vaccine induced strong HA-specific IgG responses, whereas IM delivery did not. Upon challenge with a homologous H1N1 virus, all HD-MAP-vaccinated mice were protected from weight loss, while 50% of intramuscularly vaccinated mice met humane endpoints. These findings support the use of HD-MAPs to overcome delivery limitations of DNA vaccines and enhance their utility for future outbreak and pandemic response.