LAUSR

Abstract The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e‐tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulate into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin‐applied dissolving 4M2e‐tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine‐prime alone. Compared with an intramuscular injection boost, mice receiving the MNP boost showed significantly enhanced cellular immune responses, hemagglutination‐inhibition (HAI) titers, and neutralization titers. Increased frequency of antigen‐specific plasma cells and long‐lived bone marrow plasma cells was detected in the MNP boosted group as well, indicating that skin vaccination with 4M2e‐tFliC facilitated a long‐term antibody‐mediated immunity. The 4M2e‐tFliC MNP‐boosted group also possessed enhanced protection against high lethal dose challenges against homologous A/PR/8/34 and A/Aichi/2/68 viruses and protection for a majority of immunized mice against a heterologous A/California/07/2009 H1N1 virus. High levels of M2e specific immune responses were observed in the 4M2e‐tFliC MNP‐boosted group as well. These results demonstrate that a skin‐applied 4M2e‐tFliC MNP boosting immunization to seasonal vaccine recipients may be a rapid approach for increasing the protective efficacy of seasonal vaccines in response to a significant drift seen in circulating viruses. The results also provide a new perspective for future exploration of universal influenza vaccines. Graphical abstract Figure. No Caption available.