A Single-Dose Intramuscular Immunization of Pigs with Lipid Nanoparticle DNA Vaccines Based on the Hemagglutinin Antigen Confers Complete Protection against Challenge Infection with the Homologous Influenza Virus Strain
Authors: The N. Nguyen, Sushmita Kumari, Sarah Sillman, Jayeshbhai Chaudhari, Danh C. Lai, Hiep L. X. Vu
The Influenza A virus of swine (IAV-S) is highly prevalent and causes significant economic losses to swine producers. Due to the highly variable and rapidly evolving nature of the virus, it is critical to develop a safe and versatile vaccine platform that allows for frequent updates of the vaccine immunogens to cope with the emergence of new viral strains. The main objective of this study was to assess the feasibility of using lipid nanoparticles (LNPs) as nanocarriers for delivering DNA plasmid encoding the viral hemagglutinin (HA) gene in pigs. The intramuscular administration of a single dose of the LNP-DNA vaccines resulted in robust systemic and mucosal responses in pigs. Importantly, the vaccinated pigs were fully protected against challenge infection with the homologous IAV-S strain, with only 1 out of 12 vaccinated pigs shedding a low amount of viral genomic RNA in its nasal cavity. No gross or microscopic lesions were observed in the lungs of the vaccinated pigs at necropsy. Thus, the LNP-DNA vaccines are highly effective in protecting pigs against the homologous IAV-S strain and can serve as a promising platform for the rapid development of IAV-S vaccines.
Figure
Lung pathology and presence of virus-infected cells in tissue samples. (A) Representative photos of lungs taken during necropsy. Black arrows indicate areas of the lungs with typical consolidation caused by IAV-S. The graph indicates the percentage of lung consolidation calculated based on the weighted proportions of each lobe to the total lung volume. (B) Representative images (10×) of lung sections stained with H&E and the composite microscopic lesion scores. (C) Representative images (5×) of lung sections stained with ISH to detect viral NP mRNA transcript and the composite ISH scores. (D) Representative images (5×) of tracheal sections stained with ISH to detect viral NP mRNA transcript and the composite ISH scores. Scale bar = 100 μm. * p ≤ 0.05, ** p ≤ 0.01, **** p ≤ 0.0001.
Vaccines2023, 11(10), 1596; https://doi.org/10.3390/vaccines11101596