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新型纳米颗粒包裹 MSP-1 C 末端疟疾 DNA 疫苗经不同途径免疫原性。

Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration.

机构信息

Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University 1-12-4 Sakamoto, 852-8523, Japan.

出版信息

Vaccine. 2011 Nov 8;29(48):9038-50. doi: 10.1016/j.vaccine.2011.09.031. Epub 2011 Sep 20.

Abstract

An important aspect in optimizing DNA vaccination is antigen delivery to the site of action. In this way, any alternative delivery system having higher transfection efficiency and eventual superior antibody production needs to be further explored. The novel nanoparticle, pDNA/PEI/γ-PGA complex, is one of a promising delivery system, which is taken up by cells and is shown to have high transfection efficiency. The immunostimulatory effect of this novel nanoparticle (NP) coated plasmid encoding Plasmodium yoelii MSP1-C-terminus was examined. Groups of C57BL/6 mice were immunized either with NP-coated MSP-1 plasmid, naked plasmid or NP-coated blank plasmid, by three different routes of administration; intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c). Mice were primed and boosted twice at 3-week intervals, then challenged 2 weeks after; and 100%, 100% and 50% mean of survival was observed in immunized mice with coated DNA vaccine by i.p., i.v. and s.c., respectively. Coated DNA vaccine showed significant immunogenicity and elicited protective levels of antigen specific IgG and its subclass antibody, an increased proportion of CD4(+) and CD8(+) T cells and INF-γ and IL-12 levels in the serum and cultured splenocyte supernatant, as well as INF-γ producing cells in the spleen. We demonstrate that, NP-coated MSP-1 DNA-based vaccine confers protection against lethal P. yoelii challenge in murine model across the various route of administration and may therefore, be considered a promising delivery system for vaccination.

摘要

在优化 DNA 疫苗接种方面,一个重要的方面是将抗原递送到作用部位。在这方面,任何具有更高转染效率和最终更高抗体产生的替代递药系统都需要进一步探索。新型纳米颗粒,pDNA/PEI/γ-PGA 复合物,是一种有前途的递药系统,它被细胞摄取,并显示出很高的转染效率。新型纳米颗粒(NP)包被的编码疟原虫 yoelii MSP1-C 末端的质粒的免疫刺激作用已被研究。用三种不同的给药途径:静脉内(i.v.)、腹腔内(i.p.)和皮下(s.c.)分别给 C57BL/6 小鼠免疫 NP 包被的 MSP-1 质粒、裸质粒或 NP 包被的空白质粒。免疫后 3 周间隔进行一次加强免疫,然后在 2 周后进行攻击;免疫小鼠的 i.p.、i.v.和 s.c.途径的平均存活率分别为 100%、100%和 50%。包被 DNA 疫苗显示出显著的免疫原性,并引发了针对抗原特异性 IgG 及其亚类抗体的保护性水平,增加了 CD4(+)和 CD8(+)T 细胞的比例,以及血清和培养脾细胞上清液中的 INF-γ和 IL-12 水平,以及脾中的 INF-γ产生细胞。我们证明,NP 包被的 MSP-1 DNA 疫苗在各种给药途径的小鼠模型中提供了针对致死性 P. yoelii 攻击的保护作用,因此,可被视为一种有前途的疫苗接种递药系统。

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