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bioRxiv · 10.1101/2025.06.23.661193

A single extracellular vesicle-based platform supporting both RBD protein and mRNA vaccination against SARS-CoV-2

Chung, J.·Kim, K. H.·An, S. H.·Bae, D.·Kim, J. H.·Kwon, K.·Kim, S.-H.
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Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syn-drome coronavirus 2 (SARS-CoV-2) has highlighted the need for novel, effective, and safe vaccine platforms. Extracellular vesicles (EVs) facilitate cell-to-cell communication and can modulate immune responses by delivering antigens. Here, we propose a versatile EV-based vaccine plat-form in which immune-stimulating EVs, engineered using acoustic shock waves (SW), are used to deliver either protein or mRNA antigens. Immunostimulatory EVs derived from LPS-activated THP-1 monocytes (aTEVs) were loaded with SARS-CoV-2 receptor-binding domain (RBD) protein or RBD-encoding mRNA via SW post-loading. Both aTEV-RBD-Pro and aTEV-RBD-mRNA elicited robust RBD-specific humoral and cellular immune responses in mice without the need for external adjuvants. Moreover, lyophilized aTEV-RBD-Pro vaccines retained immunogenicity after storage, supporting their chain-independent stability. These results demonstrate that a single EV-based platform can independently support both protein- and mRNA-based vaccination, highlighting its flexibility for next-generation vaccine development.

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Chung, J., Kim, K. H., An, S. H., Bae, D., Kim, J. H., Kwon, K., Kim, S.-H.. 2025-06-25. A single extracellular vesicle-based platform supporting both RBD protein and mRNA vaccination against SARS-CoV-2. https://doi.org/10.1101/2025.06.23.661193

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