Chinese researchers have developed an innovative and stable mRNA-based vaccine system in lipid nanoparticles (LNPs) administered via dissolvable microneedles (MNs). The system (mLNP-man-MN) was specifically optimized for mannose-modified LNPs (mLNP-man) encoding mRNA for the receptor-binding domain of the SARS-CoV-2 spike protein.
The vaccine system was created using 3D printing and polydimethylsiloxane micromolding techniques. It consists of a dissolvable polymer blend that was tested and optimized for high bioactivity in vitro. The microneedles maintain the physicochemical properties and bioactivity of the mRNA-LNP complex even when stored at 4°C for at least one month or at 25°C for two weeks.
Compared to conventional mRNA vaccines, which require ultra-cold chain transport and administration by healthcare professionals, this system is easy to manufacture and widely applicable – an advantage particularly for developing countries.
The microneedles specifically target the epidermis and dermis, which are rich in antigen-presenting cells. This triggers effective innate immune responses. In mice, the system induced strong systemic humoral immune responses as well as multifunctional cellular immunity in the spleen. Compared to intramuscular injection, it also generated some pulmonary T-cell response, thereby offering some protection against lung infection by SARS-CoV-2 pseudoviruses.
The study was published in the journal Acta Pharmaceutica Sinica B (Volume 16, Issue 1, 2026, pages 503–521). The authors, including Xiaoxuan Hong, Aiping Zheng, and colleagues from the Chinese Academy of Medical Sciences and other institutions, emphasize the stability and the improved immune response due to mannose modification and targeted skin application.
The findings could facilitate the development of mRNA vaccines for future pandemics by reducing storage and administration barriers. The graphical abstract is available online.
