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A "Plug-And-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-Binding Domain
Published on: July 25, 2022
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Inhalable dry powder mRNA vaccines based on extracellular vesicles
Kristen D Popowski1,2, Adele Moatti2,3, Grant Scull2,3
1Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC 27607, USA.
Matter
|July 18, 2022
Summary
Lung-derived extracellular vesicles (Lung-Exos) offer a stable, inhalable drug delivery system for respiratory diseases. These exosomes show improved lung distribution and immune response compared to synthetic liposomes.
Area of Science:
- Biotechnology
- Nanomedicine
- Pulmonology
Background:
- Respiratory diseases pose a significant global health challenge, with current therapeutics facing limitations in lung bioavailability and stability.
- Developing effective drug delivery systems for pulmonary administration is crucial for treating lung conditions.
Purpose of the Study:
- To develop room-temperature-stable, inhalable extracellular vesicles (Lung-Exos) derived from lungs for mRNA and protein drug delivery.
- To compare the efficacy of Lung-Exos with synthetic liposomes (Lipos) for pulmonary drug delivery and vaccine applications.
Main Methods:
- Lung-derived extracellular vesicles (Lung-Exos) were engineered as carriers for mRNA and protein drugs.
- Lung-Exos and liposomes (Lipos) were loaded with mRNA encoding SARS-CoV-2 spike protein.
- Inhalable dry powder formulations were administered to rodents and nonhuman primates (NHPs).
- Distribution, stability, and immunogenicity (IgG, SIgA) were assessed and compared between Lung-Exos and Lipos.
Main Results:
- Inhalable Lung-Exos demonstrated superior distribution to the bronchioles and parenchyma compared to Lipos.
- Lung-Exos successfully delivered mRNA and protein payloads to the lungs of rodents and NHPs via dry powder inhalation.
- mRNA-loaded Lung-Exos (S-Exos) elicited a stronger IgG and secretory IgA immune response than mRNA-loaded Lipos (S-Lipo).
- S-Exos maintained functionality after one month of room-temperature storage, highlighting enhanced stability.
Conclusions:
- Extracellular vesicles, specifically Lung-Exos, represent a promising and superior alternative to synthetic liposomes for inhaled mRNA drug delivery.
- Lung-Exos offer enhanced pulmonary distribution, stability, and immunogenicity, addressing key limitations of current therapeutic strategies for respiratory diseases.
