Publication date: Jun 09, 2025

mRNA vaccines have emerged as a pivotal tool to respond to global pandemics like SARS-CoV-2. However, RNA vaccines face challenges with limited duration of immunogenicity and reliance on a special cold-chain for long term storage. Self-amplifying (saRNA) vaccines have shown sustained antigen expression and durable immune responses. Herein we developed lyophilization formulations for a SARS-CoV-2 saRNA ionizable lipid nanoparticle (LNP) to help reduce dependence on the cold chain. Our results show the induction of robust immune responses in mice by saRNA-LNPs when delivered either intramuscularly or intradermally following lyophilization and storage for up to 15 weeks at above freezing temperatures. Additionally, lyophilized saRNA-LNPs were efficiently delivered into the skin via microfluidic microarray patches (M-MAPs), inducing strong humoral and cellular immunity. M-MAPs offer a painless, self-administered alternative to traditional injections for transdermal drug delivery. Our work highlights the potential for a thermostable, self-administered RNA-LNP vaccine to improve vaccine coverage.

Semantics

Original Article