Abstract
Abstract The skin contains a high density of antigen presenting cells making it an attractive target for vaccine delivery. However, the remarkable barrier function of the skin continues to present a formidable obstacle to topical vaccine delivery. To overcome this barrier we designed carboxy-methyl cellulose microneedle arrays (MNAs) to topically deliver antigens and adjuvants into the skin. MNAs were designed and fabricated to enable advantages in penetration, delivery, and diversity of biocompatibility over existing skin delivery technologies. Initially we fabricated MNAs with integrated tracer antigens. Following MNA immunization labeled antigens were identified in dendritic cells in human and murine skin, and in the draining lymph nodes of immunized animals. To evaluate immunogenicity, we incorporated the model antigen OVA in combination with various adjuvants into MNAs. MNA-mediated delivery of low dose antigen/adjuvant induced potent and durable CTL responses compared to those generated by traditional intradermal immunization. Further, MNA immunization utilizing B16 tumor cell lysates as a source of antigen induced B16 specific DTH reactions and inhibited tumor growth in a B16 tumor model. Taken together, these results demonstrate the feasibility of the use of CMC microneedle arrays for cutaneous immunization and suggest potentially broad applicability for the co-delivery of structurally diverse antigens and adjuvants.
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