Targeting Respiratory Viruses: The Efficacy of Intranasal mRNA Vaccination in Generating Protective Mucosal and Systemic Immunity Against Influenza A (H1N1)

ABSTRACT Four significant influenza outbreaks have occurred over the past 100 years, and the 1918 influenza pandemic is the most severe. Since influenza viruses undergo antigenic evolution, they are the pathogens most likely to trigger a new pandemic shortly. Intranasal vaccination offers a promising strategy for preventing diseases triggered by respiratory viruses by eliciting an immunoglobulin A (IgA) response, limiting virus replication and transmission from the respiratory tract more efficiently than intramuscular vaccines. Combining intranasal administration and mRNA‐lipid nanoparticles can be an ideal strategy for limiting the extent of the next flu pandemic. This study explored the immunogenicity of intranasally delivered mRNA encapsulated in mannose‐histidine‐conjugated chitosan lipid nanoparticles (MHCS‐LNPs) as a vaccine against influenza A (H1N1) in BALB/c mice. Intranasal administration of mRNA‐MHCS‐LNPs resulted in the generation of influenza A (H1N1) hemagglutinin‐specific neutralizing antibodies in vaccinated animals. The enzyme‐linked immunosorbent assay (ELISA) results indicated a notable increase in the quantity of immunoglobulin G (IgG) and IgA antibodies in serum and the bronchoalveolar lavage fluid (BALF), respectively, and exhibited influenza A‐specific IFN‐γ secretion in vaccinated mice, as well as a noticeable alteration in IL‐5 production. Overall, this study demonstrated an effective immunogenic response against respiratory viral infections through intranasal delivery of an mRNA‐MHCS‐LNP vaccine.