An innovative research endeavor by a team at Ludwig Maximilian University (LMU), led by Professor Olivia M. Merkel, has resulted in the development of a new system that significantly enhances the delivery of inhalable mRNA vaccines. Published in the journal Cell Biomaterials, the study showcases a hybrid polymer nanocarrier system combining poly(lactic-co-glycolic acid) (PLGA) and poly(β-amino esters) (PBAEs), aimed at addressing critical biological barriers encountered in the lungs.

Overcoming Biological Barriers

Effective mucosal vaccination via inhalation relies on carrier systems that can adeptly penetrate airway mucus while ensuring the delicate RNA molecules remain intact. As elucidated by Professor Merkel, “Once the lung barrier is overcome, the nanocarriers must escape from tiny vesicles (endosomes) that are transporting them and efficiently introduce (transfect) the mRNA into immune cells, which subsequently present the corresponding antigens on their surface.” This dual function is vital for eliciting a robust immune response.

Stable and Efficient Transport System

The LMU research team has engineered a transport system that operates through a spatiotemporally coordinated mechanism, demonstrating remarkable efficiency at transfecting targeted immune system cells. This is a crucial requirement for robust immune activation. The nanoparticles have shown a notable ability to:

  • Cross biological barriers effectively.
  • Facilitate mRNA expression in ex vivo human precision-cut lung slices, a highly pertinent human lung model.
  • Support both antigen presentation and immune cell maturation.

Following aerosolization, the PLGA/PBAE nanocarriers maintained higher transfection efficiency compared to currently approved lipid nanoparticles, marking them as suitable candidates for inhaled vaccine applications.

Advantages of the New System

The robustness of the new hybrid system presents several advantages:

Feature PLGA/PBAE Nanocarriers Lipid Nanoparticles
Transfection Efficiency Higher post-aerosolization Lower post-aerosolization
Barrier Penetration Effective Moderate
Robustness During Storage Excellent Variable

Contributions to Vaccine Development

The findings contribute significantly to the field of vaccine development, particularly in creating safe and effective mucosal vaccines. According to the study, the hybrid carrier platform not only presents a promising alternative to lipid nanoparticles but also exemplifies how data-driven polymer design can tackle numerous delivery challenges concurrently. "Our findings show that data-driven polymer design can address multiple delivery barriers simultaneously," states Merkel.

“This hybrid platform offers a promising alternative to lipid nanoparticles for next-generation pulmonary mRNA vaccines.” – Professor Olivia M. Merkel

Conclusion

The advancement of polymer-based carrier systems, such as those developed by the LMU research team, paves the way for improved delivery methods of inhalable mRNA vaccines. By efficiently overcoming biological barriers, protecting sensitive RNA, and promoting immune response, these nanocarriers hold potential for enhancing public health initiatives through innovative vaccination strategies.

Literature Cited

Min Jiang et al, A hybrid polymeric system for pulmonary mRNA delivery: Advancing mucosal vaccine development, Cell Biomaterials (2026), DOI: 10.1016/j.celbio.2025.100311.

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