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脂质纳米颗粒包裹的编码非洲猪瘟病毒p54抗原的DNA疫苗在猪体内引发强烈免疫反应。

Lipid nanoparticle-encapsulated DNA vaccine encoding African swine fever virus p54 antigen elicits robust immune responses in pigs.

作者信息

Lai Danh C, Nguyen The N, Poonsuk Korakrit, McVey D Scott, Vu Hiep L X

机构信息

Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln NE 68583, USA; School of Veterinary Medicine and Biomedical Sciences University of Nebraska-Lincoln, Lincoln NE 68583, USA.

Washington Animal Disease Diagnostic Laboratory, College of Veterinary Medicine, Washington State University, Pullman, WA 99164. USA.

出版信息

Vet Microbiol. 2025 Jun;305:110508. doi: 10.1016/j.vetmic.2025.110508. Epub 2025 Apr 7.

DOI:10.1016/j.vetmic.2025.110508
PMID:40250107
Abstract

African swine fever virus (ASFV) is one of the most significant viral pathogens affecting swine production worldwide. While several live attenuated ASF vaccines have been approved for clinical application in certain countries, there is a concern that the vaccine viruses might revert to virulence. Subunit vaccines containing one or a few viral immunogens provide a safer alternative. DNA plasmids are highly stable, easy to produce in large quantities at low cost, and safe for use in animals. However, unencapsulated DNA vaccines often exhibited low immunogenicity, largely due to the inefficient cellular entry of the plasmid DNA, leading to low protein expression. In this study, we used ASFV p54 as a model antigen to investigate the feasibility of using lipid nanoparticles (LNP) as nanocarriers to enhance the immunogenicity of DNA vaccines. Pigs immunized with the p54 LNP-DNA vaccine elicited high titers of p54-specific antibodies and T-cell responses after the second immunization. Using ELISAs based on an overlapping peptide library, we identified three antigenic areas within p54. Additionally, we noted that pigs vaccinated with the p54 LNP-DNA vaccine exhibited a similar antibody profile as those vaccinated with an experimental live attenuated vaccine or infected with a wild-type ASFV strain. The results highlight the promising potential of LNP-DNA as an effective platform for developing gene-based vaccines against ASFV.

摘要

非洲猪瘟病毒(ASFV)是影响全球养猪业的最重要病毒病原体之一。虽然几种减毒活ASFV疫苗已在某些国家获批用于临床,但人们担心疫苗病毒可能会恢复毒力。含有一种或几种病毒免疫原的亚单位疫苗提供了一种更安全的选择。DNA质粒高度稳定,易于低成本大量生产,且对动物使用安全。然而,未封装的DNA疫苗通常免疫原性较低,这主要是由于质粒DNA进入细胞的效率低下,导致蛋白质表达水平低。在本研究中,我们以ASFV p54作为模型抗原,研究使用脂质纳米颗粒(LNP)作为纳米载体来增强DNA疫苗免疫原性的可行性。用p54 LNP-DNA疫苗免疫的猪在第二次免疫后产生了高滴度的p54特异性抗体和T细胞反应。使用基于重叠肽库的ELISA,我们在p54内鉴定出三个抗原区域。此外,我们注意到用p54 LNP-DNA疫苗接种的猪表现出与用实验性减毒活疫苗接种或感染野生型ASFV毒株的猪相似的抗体谱。这些结果突出了LNP-DNA作为开发抗ASFV基因疫苗的有效平台的潜在前景。

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