An engineered intradermal microneedle-array device enhances the cellular immune responses in a guinea pig model

Introduction: Intradermal (ID) vaccination can be highly immunogenic due to the density of antigen-presenting cells in the skin, but reliable ID delivery remains technically challenging. We evaluated a programmable microneedle-array intradermal injector, InocuJect, designed to distribute vaccine micro-deposits across a defined dermal area. Methods: In female Hartley guinea pigs, we compared vaccination with the automated ID device to conventional Mantoux intradermal injection followed by electroporation (ID+EP) using two vaccine platforms: a DNA vaccine encoding SARS-CoV-2 spike (pIDV-II-SARS-CoV-2) and the licensed virus-like particle vaccine GARDASIL®9. Results: For the DNA vaccine, both methods induced spike-specific and pseudovirus-neutralizing responses by day 56, with similar neutralizing titers between groups. For GARDASIL®9, both delivery methods generated comparable HPV16 L1-specific IgG at the final time points. In contrast, the automated ID device induced stronger antigen-specific cellular responses, as reflected by increased IFN-γ RNA and protein levels following peptide stimulation. Conclusions: These findings suggest that spatially distributed dermal delivery using a microneedle-array-based intradermal injector is associated with enhanced IFN-γ-based cellular immune readouts, while maintaining robust humoral responses across distinct vaccine platforms.