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固体脂质纳米粒递送编码尿素酶 A 亚单位的 DNA 疫苗:感染小鼠模型前后的免疫分析。

Solid Lipid Nanoparticles Delivering a DNA Vaccine Encoding Urease A Subunit: Immune Analyses before and after a Mouse Model of Infection.

机构信息

School of Science, RMIT University, 264 Plenty Road, Bundoora, VIC 3083, Australia.

Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia.

出版信息

Int J Mol Sci. 2024 Jan 16;25(2):1076. doi: 10.3390/ijms25021076.

Abstract

In this study, novel solid lipid particles containing the adjuvant lipid monophosphoryl lipid A (termed 'SLN-A') were synthesised. The SLN-A particles were able to efficiently bind and form complexes with a DNA vaccine encoding the urease alpha subunit of . The resultant nanoparticles were termed lipoplex-A. In a mouse model of infection, the lipoplex-A nanoparticles were used to immunise mice, and the resultant immune responses were analysed. It was found that the lipoplex-A vaccine was able to induce high levels of antigen-specific antibodies and an influx of gastric CD4 T cells in vaccinated mice. In particular, a prime with lipoplex-A and a boost with soluble UreA protein induced significantly high levels of the IgG1 antibody, whereas two doses of lipoplex-A induced high levels of the IgG2c antibody. In this study, lipoplex-A vaccination did not lead to a significant reduction in colonisation in a challenge model; however, these results point to the utility of the system for delivering DNA vaccine-encoded antigens to induce immune responses and suggest the ability to tailor those responses.

摘要

在这项研究中,合成了含有佐剂脂质单磷酰脂质 A(称为“SLN-A”)的新型固体脂质颗粒。这些 SLN-A 颗粒能够有效地与编码 尿素酶 α 亚单位的 DNA 疫苗结合并形成复合物。所得的纳米颗粒称为脂质体 A。在 感染的小鼠模型中,使用脂质体 A 纳米颗粒对小鼠进行免疫,并分析了产生的免疫反应。结果发现,脂质体 A 疫苗能够诱导接种小鼠产生高水平的抗原特异性抗体和胃 CD4 T 细胞涌入。特别是,脂质体 A 进行初免和可溶性 UreA 蛋白进行加强免疫可诱导高水平的 IgG1 抗体,而两剂脂质体 A 可诱导高水平的 IgG2c 抗体。在这项研究中,脂质体 A 疫苗接种并没有在挑战模型中导致定植的显著减少;然而,这些结果表明该系统用于传递 DNA 疫苗编码抗原以诱导免疫反应的有效性,并表明能够调整这些反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a97/10816323/e8d828804640/ijms-25-01076-g001.jpg

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