Table 2.

Representative delivery strategies for RNA vaccines.

Delivery system	Key advantages	Main translational challenges	Representative notes/examples
Lipid nanoparticles (LNPs)	Highest clinical maturity; efficient encapsulation, uptake, and endosomal escape; adaptable lipid chemistry.	Reactogenicity, biodistribution control, PEG-related concerns, and continued optimization of potency versus tolerability.	Core platform for approved COVID-19 mRNA vaccines; intense work on ionizable lipids and PEG alternatives (92–101).
Hydrogel depots	Sustained antigen release, prolonged germinal-center stimulation, and opportunities for local immune programming.	Limited clinical data and more complex manufacturing for specialized depot architectures.	Attractive for dose sparing or single-dose strategies and for therapeutic vaccines (102–105).
Microneedle patches	Needle-sparing, skin-targeted delivery, improved convenience, and potential thermostability benefits with dried formulations.	Patch fabrication, formulation stability, and consistent skin delivery across users require further optimization.	May improve access, facilitate simplified administration records, and support skin/APC-targeted vaccination approaches (106, 107, 182).
Nanoemulsions/mucosal carriers	Can improve immune programming, APC recruitment, and possibly mucosal targeting in future respiratory vaccines.	Formulation stability, reproducibility, and translational evidence remain less mature than for LNPs.	Most useful as emerging adjunctive or specialized delivery formats rather than replacements for LNPs (80–82, 108, 109).