Vaccination with influenza hemagglutinin-loaded ceramic nanoporous microneedle arrays induces protective immune responses

Abstract

Microneedle arrays (MNAs) are a promising mean to administer vaccines. Without the need of highly trained personnel, MNAs can be applied to deliver vaccines into the dermis, which is well equipped to initiate potent immune responses. While vaccination using dissolving microneedle arrays has been extensively investigated, the use of solid nanoporous MNAs (npMNAs) to deliver vaccines remained largely unexplored. In this report we investigated whether npMNAs with an average pore size of 80 nm, can be used for influenza vaccination based on recombinant hemagglutinin (HA) protein of the 2009 pandemic H1N1 (pH1N1) virus. Fluorescently labeled HA loaded in the npMNAs was effectively delivered into the skin of mouse ears, as a result of a diffusion-based process. Compared to intramuscular immunization, intradermal HA vaccination of mice using npMNAs elicited high levels of HA antigen specific antibodies, with pH1N1 hemagglutination inhibition and neutralization activity. Moreover, mice vaccinated with pH1N1 HA loaded npMNAs were completely protected against a potentially lethal challenge with mouse adapted pH1N1 virus. These results illustrate that intradermal subunit vaccine immunization using npMNAs is a promising approach to facilitate effective vaccination.