Lyophilized SARS-CoV-2 self-amplifying RNA vaccines for microneedle array patch delivery

Madison M Driskill; Ian A Coates; Paul J Hurst; Netra U Rajesh; Maria T Dulay; Robert M Waymouth; Wataru Akahata; Kenta Matsuda; Jonathan F Smith; Gunilla B Jacobson; Jillian L Perry; Shaomin Tian; Joseph M DeSimone

doi:10.1016/j.jconrel.2025.113944

Lyophilized SARS-CoV-2 self-amplifying RNA vaccines for microneedle array patch delivery

J Control Release. 2025 Jun 9:384:113944. doi: 10.1016/j.jconrel.2025.113944. Online ahead of print.

Authors

Affiliations

¹ Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
² Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
³ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Radiology, Stanford University, Stanford, CA 94305, USA.
⁵ VLP Therapeutics, Inc., Gaithersburg, MD 20878, USA; VLP Therapeutics Japan, Inc., Nishi-Shinbashi, Minato-ku, Tokyo 105-0003, Japan.
⁶ VLP Therapeutics, Inc., Gaithersburg, MD 20878, USA.
⁷ Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA.
⁸ Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: smtian@email.unc.edu.
⁹ Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Radiology, Stanford University, Stanford, CA 94305, USA. Electronic address: jmdesimone@stanford.edu.

PMID: 40499765
DOI: 10.1016/j.jconrel.2025.113944

Abstract

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.

Keywords: Covid-19; Lyophilization; Microneedle; Self-amplifying RNA; Vaccines.