Lipid nanoparticle-encapsulated DNA vaccine confers protection against swine and human-origin H1N1 influenza viruses
Authors: The N. Nguyen, Danh C. Lai, Sarah Sillman, Erika Petro-Turnquist, Eric A. Weaver, and Hiep L. X. Vu
Abstract
In 2009, a novel swine-origin H1N1 virus emerged, causing a pandemic. The virus, known as H1N1pdm09, quickly displaced the circulating H1 lineage and became the dominant seasonal influenza A virus subtype infecting humans. Human-to-swine spillovers of the H1N1pdm09 have occurred frequently, and each occurrence has led to sustained transmission of the human-origin H1N1pdm09 within swine populations. In the present study, we developed a lipid nanoparticle-based DNA vaccine (LNP-DNA) containing the hemagglutinin gene of a swine-origin H1N1pdm09. In pigs, this LNP-DNA vaccine induced a robust antibody response after a single intramuscular immunization and protected the pigs against challenge infection with the homologous swine-origin H1N1pdm09 virus. In a mouse model, the LNP-DNA vaccine induced antibody and T-cell responses and protected mice against lethal challenge with a mouse-adapted human-origin H1N1pdm09 virus. These findings demonstrate the potential of the LNP-DNA vaccine to protect against both swine- and human-origin H1N1pdm09 viruses.
Fig. Physicochemical characteristics and the stability of the LNP-DNA vaccine. (A) Average diameter, (B) polydispersity index, (C) zeta potential, and (D) encapsulation efficiency of the LNP-DNA freshly prepared or stored at 4°C or room temperature (RT) over 56 days. Data were obtained from two independent LNP-DNA constructs. (E) Transfection efficiency in HEK-293T cells of LNP-DNA when freshly prepared or stored at 4°C or room temperature for 56 days. Scale bar = 100 μm. Data presented in this figure were obtained from two independent experiments.
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Keywords: lipid nanoparticles; DNA vaccine; influenza A virus; H1n1pdm09; immunotherapy; Flex-M
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