Single-Administration Polymeric Microneedles for Prime-and-Boost Vaccination Against Hepatitis B Through Biphasic Antigen Delivery

Hepatitis B vaccination commonly requires multiple administrations to achieve durable protective immunity, creating challenges for patient compliance and vaccination coverage. To address this limitation, a polymeric microneedle platform capable of generating both immediate and prolonged antigen exposure following a single application was developed.
The system was designed using biodegradable polylactic acid (PLA) microneedle tips as a long-acting antigen reservoir, a rapidly dissolving carboxymethyl cellulose (CMC) coating for early antigen availability, and a polyvinyl alcohol/polyvinylpyrrolidone (PVA/PVP) supporting layer that dissolved after skin insertion to implant the antigen-loaded PLA tips into the skin. Hepatitis B surface antigen (HBsAg) was incorporated into both release compartments to establish a biphasic delivery profile.
The fabricated polymeric microneedles exhibited sufficient mechanical integrity for skin insertion and successfully deposited both antigen-containing components into porcine skin. Following application, the PVA/PVP layer rapidly dissolved, enabling separation of the PLA tips from the backing structure. Release studies demonstrated distinct delivery phases, characterized by rapid antigen availability from the CMC compartment and prolonged release from the implanted PLA matrix for several weeks.
The immunological performance of the system was evaluated in mice after a single administration. Antibody responses generated by the dual-compartment polymeric microneedles were comparable to, or greater than, those induced by conventional multi-dose vaccination regimens. These findings suggest that sequential antigen exposure achieved through a single application can reproduce the immunological benefits of separate prime and booster vaccinations.
This study demonstrates the potential of polymeric microneedles as a single-administration vaccination platform capable of reducing dosing frequency while maintaining robust immune responses.