CHINESE JOURNAL OF MEDICINAL GUIDE >
An Influenza Hemagglutinin mRNA Lipid Nanoparticle Vaccine Elicits Respiratory Mucosal Immunity
Received date: 2026-02-26
Revised date: 2026-03-26
Accepted date: 2026-04-20
Online published: 2026-06-29
Objective： To investigate mRNA mucosal influenza vaccines， develop mRNA lipid nanoparticles （LNPs） based on influenza virus hemagglutinin （HA）， and assess their immunogenicity and safety through nebulized inhalation.Methods： mRNA encoding HA was synthesized via in vitro transcription， and LNPs encapsulating HA mRNA were prepared using microfluidic technology. The optimal formulation was identified based on the physicochemical properties and cell transfection efficiency of the LNPs. Additionally， the lysosomal escape capability， cell uptake mechanisms， and cytotoxicity of the LNPs were investigated. Mice were immunized via both intramuscular injection and pulmonary nebulized inhalation. The humoral and respiratory mucosal immune responses elicited were compared， and the general safety of the vaccine was preliminarily assessed.Results： The transfection efficiency of the synthesized HA mRNA in cells using transfection reagents was 77.6%. Following encapsulation in LNPs， the cell transfection efficiency of the optimal LNP formulation， characterized by a nitrogen-phosphorus ratio of 8∶1， exceeded 90%. Effective lysosomal escape occurred within 6 h， with the uptake pathway reliant on endocytosis mediated by dynamin and caveolin-1. After nebulized inhalation immunization in mice， high levels of HA-specific serum IgG antibodies were induced， alongside the production of mucosal immune IgA antibodies. Throughout the immunization period， the mice exhibited a steady increase in body weight， with no abnormalities detected in serum biochemical indicators and no significant pathological damage observed in vital organs.Conclusion： The HA mRNA synthesized in this study demonstrates the capacity to translate and express proteins. The optimal HA mRNA-LNPs that were prepared and screened exhibit excellent cell delivery efficiency and antigen expression capability in vitro， effectively stimulating robust humoral and mucosal dual immunity in vivo， while also ensuring good safety.
LOU Jinghu, WU Zhineng, CHENG Yi, LI Meng, LIU Nan, WANG Zengming, GAO Xiang, ZHENG Aiping, ZHANG Hui
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An Influenza Hemagglutinin mRNA Lipid Nanoparticle
Vaccine Elicits Respiratory Mucosal Immunity
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