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纳米疫苗针对核糖体 P2 蛋白，纳米材料作为弓形虫有希望的 DNA 疫苗。

Nano vaccines for Ribosomal P2 Protein With Nanomaterials as a Promising DNA Vaccine Against Toxoplasmosis.

机构信息

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

出版信息

Front Immunol. 2022 Feb 21;13:839489. doi: 10.3389/fimmu.2022.839489. eCollection 2022.

DOI:10.3389/fimmu.2022.839489
PMID:35265084
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8899214/
Abstract

Caused by , toxoplasmosis has aroused great threats to public health around the world. So far, no effective vaccine or drug is commercially available, and the demands for a safe and effective therapeutic strategy have become more and more urgent. In the current study, we constructed a DNA vaccine encoding ribosomal P2 protein (TgP2) and denoted as TgP2-pVAX1 plasmid. To improve the immunoprotection, nanomaterial poly-lactic--glycolic acid (PLGA) and chitosan were used as the delivery vehicle to construct TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres. Before vaccinations in BALB/c mice, TgP2-pVAX1 plasmids were transiently transfected into Human Embryonic Kidney (HEK) 293-T cells, and the expression of the eukaryotic plasmids was detected by laser confocal microscopy and Western blotting. Then the immunoprotection of naked DNA plasmids and their two nano-encapsulations were evaluated in the laboratory animal model. According to the investigations of antibody, cytokine, dendritic cell (DC) maturation, molecule expression, splenocyte proliferation, and T lymphocyte proportion, TgP2-pVAX1 plasmid delivered by two types of nanospheres could elicit a mixed Th1/Th2 immune response and Th1 immunity as the dominant. In addition, TgP2-pVAX1/PLGA and TgP2-pVAX1/CS nanospheres have great advantages in enhancing immunity against a lethal dose of RH strain challenge. All these results suggested that TgP2-pVAX1 plasmids delivered by PLGA or chitosan nanomaterial could be promising vaccines in resisting toxoplasmosis and deserve further investigations and applications.

摘要

弓形虫病引起的，已经对全世界的公共卫生造成了巨大威胁。到目前为止，还没有商业上可用的有效疫苗或药物，因此对安全有效的治疗策略的需求变得越来越迫切。在目前的研究中，我们构建了一种编码核糖体 P2 蛋白（TgP2）的 DNA 疫苗，并将其命名为 TgP2-pVAX1 质粒。为了提高免疫保护效果，我们使用纳米材料聚乳酸-羟基乙酸（PLGA）和壳聚糖作为递送载体，构建了 TgP2-pVAX1/PLGA 和 TgP2-pVAX1/CS 纳米球。在 BALB/c 小鼠接种疫苗之前，我们将 TgP2-pVAX1 质粒瞬时转染到人胚肾（HEK）293-T 细胞中，并通过激光共聚焦显微镜和 Western blot 检测真核质粒的表达。然后，我们在实验室动物模型中评估了裸露 DNA 质粒及其两种纳米封装的免疫保护作用。根据抗体、细胞因子、树突状细胞（DC）成熟、分子表达、脾细胞增殖和 T 淋巴细胞比例的研究，两种纳米球递送的 TgP2-pVAX1 质粒可以诱导混合 Th1/Th2 免疫反应和 Th1 免疫反应为主导。此外，TgP2-pVAX1/PLGA 和 TgP2-pVAX1/CS 纳米球在增强对 RH 株致死剂量的免疫力方面具有很大优势。所有这些结果表明，PLGA 或壳聚糖纳米材料递送的 TgP2-pVAX1 质粒可能是抵抗弓形虫病的有前途的疫苗，值得进一步研究和应用。

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