Intranasal mRNA vaccines: Targeting mucosal immunity through optimized delivery

The COVID-19 pandemic highlighted the transformative potential of mRNA lipid nanoparticle (LNP) vaccines, yet their limited ability to induce mucosal immunity at respiratory entry points remains a significant challenge. Intranasal vaccination offers a promising strategy to elicit local immune responses at the primary site of respiratory pathogen entry, critical for preventing infections like SARS-CoV-2 and influenza.1 In a recent study published in Molecular Therapy Nucleic Acids, Vu et al. demonstrated that while intranasal mRNA-LNPs efficiently transfect lung epithelial and immune cells, they fail to generate robust primary mucosal immunity, despite the success of LNPs in intramuscular applications, unless boosted in a primed context2 (Figure 1).