Thermostable unit solid dose formulations for subcutaneous administration of DNA vaccines.

Abstract

The coronavirus disease 2019 pandemic has highlighted the critical need for thermostable vaccines to ensure equitable distribution and accessibility, particularly in regions lacking cold chain infrastructure. Here we present a thermostable, solid dose DNA vaccine (SDV) platform for subcutaneous delivery, based on a sugar-sugar alcohol-polymer formulation manufactured via lyophilization and compaction. Using luciferase-expressing plasmid as a model, we demonstrate that subcutaneous vaccination with SDV formulation of C57BL/6 mice results in efficient and durable transgene expression in vivo. In vitro stability assays confirmed that the SDV formulation maintained excellent thermostability after 30 days of storage at 4°C, 25°C, 37°C, and 42°C. We next applied the SDV platform to a Zika virus (ZIKV) NS1 DNA vaccine and immunized BALB/c mice. ZIKV-SDV vaccination elicited robust NS1-specific antibody and T cell responses, and conferred protection upon ZIKV challenge. These data establish the feasibility of lyophilized SDV DNA vaccines for needle-free thermostable delivery. By eliminating the need for reconstitution, refrigeration, and skilled administration, SDV formulation has the potential to enhance the deployment, cost effectiveness, and shelf-life of DNA vaccines in resource-limited settings.