Thermostable unit solid dose formulations for subcutaneous administration of DNA vaccines

Area of Science:

• Vaccinology
• Biotechnology
• Materials Science

Background:

• The COVID-19 pandemic underscored the need for thermostable vaccines, especially for regions lacking cold chain infrastructure.
• Current vaccine distribution challenges necessitate innovative delivery platforms that are stable and accessible.

Purpose of the Study:

• To develop and evaluate a thermostable, solid dose DNA vaccine (SDV) platform for subcutaneous delivery.
• To assess the stability, efficacy, and immunogenicity of the SDV platform using model and pathogen-specific antigens.

Main Methods:

• A novel sugar-sugar alcohol-polymer formulation was developed for lyophilization and compaction into a solid dose DNA vaccine (SDV).
• In vivo studies in C57BL/6 mice assessed transgene expression from luciferase-expressing plasmid SDV.
• In vitro stability assays evaluated SDV thermostability under various storage conditions (4°C to 42°C).
• A Zika virus (ZIKV) NS1 DNA vaccine was formulated as SDV and tested in BALB/c mice for immunogenicity and protective efficacy against ZIKV challenge.

Main Results:

• SDV formulation demonstrated efficient and durable transgene expression following subcutaneous vaccination in mice.
• The SDV formulation exhibited excellent thermostability, maintaining integrity after 30 days of storage at temperatures up to 42°C.
• ZIKV-SDV vaccination induced robust NS1-specific antibody and T cell responses and provided protection against ZIKV challenge.

Conclusions:

• The lyophilized SDV DNA vaccine platform is feasible for needle-free, thermostable delivery.
• SDV technology eliminates the need for reconstitution, refrigeration, and skilled administration, enhancing vaccine deployment and cost-effectiveness.
• This platform holds significant potential for improving vaccine accessibility in resource-limited settings.