Journal of controlled release : official journal of the Controlled Release SocietyDec 8, 2025

A single extracellular vesicle platform delivering both protein and mRNA vaccines against SARS-CoV-2

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

Robust encapsulation of SARS-CoV-2 receptor-binding domain protein and mRNA into extracellular vesicles was achieved, with 69% and 75% encapsulation efficiency, respectively.

Extracellular vesicles derived from immune cells successfully encapsulated protein and mRNA antigens without losing integrity.
Both protein- and mRNA-loaded vaccines triggered strong immune responses in mice, comparable to those of conventional adjuvanted vaccines.
Neutralizing antibody levels and cytokine profiles from the EV vaccines matched or exceeded those seen with alum-adjuvanted controls.
Lyophilized EV vaccines maintained their ability to provoke an immune response after 7 days at 4 °C, indicating potential for easier storage and transport.
The SWEET platform represents a novel method for delivering either protein or mRNA vaccines effectively.

Simplified

The COVID-19 pandemic has underscored the urgent need for safe, effective, and flexible vaccine platforms. Here, we present a modular extracellular vesicle (EV)-based vaccine system engineered using Shock Wave Extracellular Vesicle Engineering Technology (SWEET)-an acoustic shock wave-based post-loading method that enables high-efficiency encapsulation of either protein or mRNA antigens into immunostimulatory EVs. Using SARS-CoV-2 receptor-binding domain (RBD) as a model antigen, we achieved robust encapsulation of RBD protein (∼69 %, relative to the initial input amount) and RBD mRNA (∼75 %, representing the Benzonase-protected fraction relative to total EV-associated mRNA) into EVs derived from LPS-activated THP-1 monocytes, without compromising vesicle integrity. Both protein- and mRNA-loaded EV vaccines elicited potent, adjuvant-free humoral and balanced Th1/Th2 cellular immune responses in mice, with neutralizing antibody titers and cytokine profiles comparable to or exceeding those of alum-adjuvanted controls. Notably, lyophilized EV vaccines retained immunogenicity after 7 days at 4 °C, supporting cold chain-independent distribution. To our knowledge, this is the first demonstration that a single post-loaded EV platform can independently deliver either functional protein or mRNA vaccines with quantifiable intracellular expression and robust immune activation. The SWEET platform's scalability, modularity, and compatibility with clinically familiar components position it as a promising next-generation vaccine and drug delivery technology.

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A single extracellular vesicle platform delivering both protein and mRNA vaccines against SARS-CoV-2

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