Differential Dual-Release Bilayer Microneedles Loaded with Aluminum Adjuvants as a Safe and Effective Vaccine Platform

Aluminum adjuvants are currently the most widely used adjuvants for human vaccines. However, concerns about their safety, such as local irritation at the vaccination site and potential neurotoxicity, have been raised over recent years. Herein, the bilayer microneedles are fabricated using commercially available materials and a simple micromolding preparation method in a differential dual-release manner for sustained antigen release in the outer layer, and fast release of aluminum in the inner layer. The outer layer here replaces aluminum adjuvants to form an antigen depot, and the rapidly released adjuvants of the inner layer can activate dendritic cells, which effectively reduces the amount of aluminum while retaining their effect. The use of ovalbumin in vivo as the model antigen demonstrates that compared with subcutaneous and intramuscular injections, the bilayer microneedles achieve effective humoral immunity and relatively balanced immune response with less aluminum (1/25 of the dose), which may be related to the mechanical adjuvant effect of the microneedles. Mice treated with the bilayer microneedles show little to no aluminum accumulation in different organs, and no local irritation such as granuloma is observed. The superior vaccination safety and strong immunity using bilayer microneedles make it a promising vaccine platform.