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NPJ Vaccines . Lipid nanoparticle-encapsulated DNA vaccine prevented lung consolidation following heterologous influenza A virus challenge in pigs

tetano

Editor, Senior Moderator
NPJ Vaccines


. 2026 May 2.
doi: 10.1038/s41541-026-01473-1. Online ahead of print.
Lipid nanoparticle-encapsulated DNA vaccine prevented lung consolidation following heterologous influenza A virus challenge in pigs

The N Nguyen[SUP] #[/SUP][SUP] 1 2 [/SUP], Danh C Lai[SUP] #[/SUP][SUP] 1 2 [/SUP], Hung Q Luong[SUP] 1 2 [/SUP], Kassandra Durazo-Martínez[SUP] 1 3 [/SUP], Sushmita Kumari[SUP] 1 2 [/SUP], Sarah Sillman[SUP] 2 [/SUP], Phillip Gauger[SUP] 4 [/SUP], Giao P Trinh[SUP] 1 [/SUP], Hiep L X Vu[SUP] 5 6 [/SUP]


Affiliations
Free article Abstract

The substantial antigenic diversity of Influenza A virus (IAV) presents significant challenges to the development of broadly protective vaccines for swine. Moreover, pigs vaccinated with whole-inactivated virus or hemagglutinin (HA) subunit vaccines may experience more severe lung consolidation than non-vaccinated pigs when exposed to antigenically mismatched IAV strains, a phenomenon known as vaccine-associated enhanced respiratory disease (VAERD). We recently developed a lipid nanoparticle-encapsulated DNA (LNP-DNA) vaccine encoding the HA of IAV, which elicited robust immune responses following a single immunization and protected pigs against homologous IAV challenges. In this study, we compared the immunogenicity and protective efficacy between the HA protein-based vaccine and the HA DNA-based vaccine against an antigenically mismatched IAV strain in pigs. Neither vaccine induced cross-reactive hemagglutination inhibition (HI) antibodies nor prevented viral shedding in nasal secretions following heterologous challenge. However, while the HA protein-based vaccine exacerbated lung lesions compared to non-vaccinated controls, the HA DNA-based vaccine prevented the development of gross lung pathology. Transcriptomic analyses revealed distinct gene expression profiles between the two vaccine groups. These findings suggest that the LNP-DNA vaccine platform may offer a safer and more effective strategy for developing vaccines against IAV in swine.


 
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