A Microneedle-Based Delivery System for Broad-Protection Seasonal Influenza A DNA Nanovaccines

Seasonal influenza A viruses continue to pose a public health threat, and current vaccines are not sufficiently effective because of virus mutation. There is an urgent need to develop a broad-protection influenza A vaccine. Our team previously designed potential universal hemagglutinin (HA) sequences against seasonal influenza A H1N1 and H3N2 (mH1 and mH3, respectively) through a mosaic strategy. In this study, we construct DNA vaccines by linking the antigens mH1 and mH3 via internal ribosome entry sites and then wrap the DNA with the deoxycholic acid-modified polyetherimide to form DNA nanovaccines. A microneedle is used to deliver DNA nanovaccines, and the data show that better cellular and cross-reactivity and protective immunity are induced compared with the intramuscular injection method. These results suggest that microneedle-based delivery of DNA nanovaccines could be a promising platform for development of a broad-protection influenza vaccine.