Respiratory viruses such as influenza, RSV, or coronaviruses enter the body via the mucous membranes of the airways. Traditional vaccines, however, are usually administered by injection and primarily trigger an immune response in the blood – not necessarily where the pathogens first invade. Experts therefore agree: to stop infections early and prevent transmission, vaccines need to elicit a protective immune response directly in the lungs. A particularly promising approach is the inhalation of mRNA vaccines. Yet significant technical hurdles remain: the fragile mRNA must penetrate the viscous mucus of the airways, reach the appropriate immune cells, and exert its effect – all after a mechanically demanding aerosolization process.
A new carrier makes mRNA vaccines inhalable
In a newly published study, DZL researchers at the CPC-M site and their team developed an innovative hybrid nanoparticle system that addresses these challenges. It combines two well-established polymers – PLGA and so-called poly(β-aminoesters) – into an intelligent delivery system for mRNA. This system protects the mRNA during its journey through the airways, enables it to penetrate lung mucus, and ensures efficient uptake by antigen-presenting immune cells. Once inside, the mRNA is released in a controlled manner and can effectively express its genetic information. Importantly, the nanoparticles remain stable and functional even after aerosolization – a critical requirement for clinical application. In preclinical models, including human lung tissue sections, the system demonstrated markedly better performance than previous comparison technologies.
Paving the way for the next generation of vaccines
The findings represent a significant step toward effective mucosal vaccines. Inhalable mRNA vaccines could not only protect against severe disease but also block infections at their entry point. This has far-reaching implications for both individual protection and pandemic control. Furthermore, the developed delivery system opens new avenues for mRNA-based therapies for lung diseases in general. The study clearly demonstrates how modern materials science and immunology can work together to advance innovative prevention and treatment strategies.
Original publication: Min Jiang et al., A hybrid polymeric system for pulmonary mRNA delivery: Advancing mucosal vaccine development, Cell Biomaterials, 2026, 100311, ISSN 3050-5623, https://doi.org/10.1016/j.celbio.2025.100311
