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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 # 1 2 , Danh C Lai # 1 2 , **** Q Luong 1 2 , Kassandra Durazo-Martínez 1 3 , Sushmita Kumari 1 2 , Sarah Sillman 2 , Phillip Gauger 4 , Giao P Trinh 1 , Hiep L X Vu 5 6
Affiliations
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.
. 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 # 1 2 , Danh C Lai # 1 2 , **** Q Luong 1 2 , Kassandra Durazo-Martínez 1 3 , Sushmita Kumari 1 2 , Sarah Sillman 2 , Phillip Gauger 4 , Giao P Trinh 1 , Hiep L X Vu 5 6
Affiliations
- PMID: 42069749
- DOI: 10.1038/s41541-026-01473-1
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.