Development and Evaluation of Dual Microneedle Array Patch for Sequential Intradermal Delivery of Adjuvant and Antigen
摘要
Adjuvants are critical for enhancing immune responses to recombinant protein-based vaccines, which typically exhibit weak immunogenicity. Microneedle array patches (MAPs) offer a promising method for intradermal delivery, but conventional Co-Delivery MAPs (containing antigen and adjuvant together) have limited loading capacity and potential undesirable interactions. Adjuvants may also trigger adverse reactions in sensitive populations. This study aimed to develop a Dual-Delivery MAP system that enables separate and sequential administration of antigens and adjuvants, addressing these limitations and supporting personalized vaccination strategies.
MethodsThe Dual-Delivery MAP was developed using a coated MAP for ovalbumin (OVA) and a dissolving MAP for the CTA1 adjuvant. Patches were sequentially applied to the same skin site. Delivery efficiency, intradermal distribution, and immunogenicity were evaluated and compared to a conventional Co-Delivery MAP and an intramuscular (IM) injection group (OVA and CTA1 in solution). OVA- and CTA1-specific IgG titers were measured to assess immune responses.
ResultsBoth Dual-Delivery and Co-Delivery MAPs demonstrated similar delivery efficiency (~ 70%). However, the Dual-Delivery MAP elicited significantly higher IgG titers against CTA1 and OVA compared to the Co-Delivery MAP, likely due to enhanced adjuvant functionality. The Dual-Delivery MAP induced immune responses comparable to IM injection, indicating that sequential delivery preserves adjuvant activity and enhances immunogenicity.
ConclusionsThe Dual-Delivery MAP represents a novel, modular approach for skin-targeted vaccination. By separating antigen and adjuvant into distinct patches, it improves stability, maintains adjuvant efficacy, and enables personalized vaccine administration, offering a promising strategy for effective and safe vaccination.