Delivery of gold nanoparticle-conjugated M2e influenza vaccine in mice using coated microneedles

Abstract

As a prospective influenza vaccination platform, a microneedle patch offers advantages such as self-administration and reduction of needle-phobia-associated vaccination avoidance. In an effort to design a broadly protective influenza vaccine we have previously developed a vaccine formulation containing the highly conserved ectodomain sequence of the M2 influenza protein (M2e) attached to the surface of gold nanoparticles (AuNPs) with CpG as a soluble adjuvant (AuNP-M2e + sCpG). Our previous studies have used the intranasal route for vaccination and demonstrated broad protection from this vaccine. Here we asked the question whether the same formulation can be effective when administered to mice using microneedles. We demonstrate that the microneedles can be coated with AuNP-M2e + sCpG formulation, and the AuNPs from the coating can be readily resuspended without aggregation. The AuNPs were delivered with high efficiency into murine skin, and the AuNPs cleared the skin within 12 h of microneedle treatment. After vaccination, strong M2e-specific humoral and cellular responses were stimulated, and the vaccinated mice were 100% protected following a lethal challenge with influenza A/PR/8/34 (H1N1).