Human skin is the first protective barrier to exposure to external agents. As a result, the immune system localized there orchestrates a potent response to pathogens. Many studies have shown that intradermal immunization is a highly effective way to get a strong immune response to vaccination. However classical intradermal immunization by needle and syringe is difficult to perform and requires specific professional skill to be done correctly. To address this problem we have developed methods of micromolding and microfabrication to design and fabricate dissolving microneedle (MN) patches which precisely deliver vaccine to the upper part of skin and do not require medical expertise to use. Our prior work has shown that MN patch immunization can induce stronger immune responses over traditional injection-based vaccination, including a successful phase 1 clinical trial of influenza vaccination. To get a stronger and more durable immune response, vaccination should be accompanied by an optimal adjuvant. However, the adjuvant should be compatible with MN patch fabrication technology. This is a challenge as many adjuvants are emulsions or microparticles which are hard to restore after drying and reconstitution, and MN patches are inherently dry formulations. Polyphosphazenes, such as poly[di(carboxylatophenoxy)phosphazene] (PCPP), have been extensively used as vaccine adjuvants and could be an option for MN patches. In this study, Ebola vaccine and PCPP were co-formulated into MN patches and tested on mice in comparison with the same dose of vaccine with or without PCPP injected intramuscularly (IM). Immunization with PCPP IM or by MN patch gave 40 times stronger antigen-specific IgG antibody response compared to vaccine injected without the adjuvant. Those responses were durable for at least 5 months. We conclude that PCPP, as adjuvant, is compatible with MN patches for enhanced immunization.

Ebola vaccination by microneedle patch with polyphosphazene adjuvant

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.