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Intranasal mRNA vaccines: Targeting mucosal immunity through optimized delivery

Achyut Pandey, Sacheen Kumar, Shruti Mishra

2025Molecular Therapy — Nucleic Acids8 citationsDOIOpen Access PDF

Abstract

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).

Topics & Concepts

Mucosal immunityNasal administrationImmunityMedicineImmunologyMessenger RNAVirologyImmune systemBiologyGeneBiochemistryRNA Interference and Gene DeliveryImmune Response and InflammationViral gastroenteritis research and epidemiology
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