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一种编码结构蛋白 prM/E 的 DNA 疫苗候选物可引发强烈的免疫反应,保护小鼠免受登革 4 型病毒感染。

A DNA vaccine candidate encoding the structural prM/E proteins elicits a strong immune response and protects mice against dengue-4 virus infection.

机构信息

Laboratory of Molecular Virology, Department of Clinical Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

出版信息

Vaccine. 2011 Jan 17;29(4):831-8. doi: 10.1016/j.vaccine.2010.10.078. Epub 2010 Nov 27.

Abstract

A DNA vaccine expressing dengue-4 virus premembrane (prM) and envelope (E) genes was produced by inserting these genes into a mammalian expression plasmid (pCI). Following a thorough screening, including confirmation of protein expression in vitro, a recombinant clone expressing these genes was selected and used to immunize BALB/c mice. After 3 immunizations all the animals produced detectable levels of neutralizing antibodies against dengue-4 virus. The cytokines levels and T cell proliferation, detected ex vivo from the spleen of the immunized mice, showed that our construction induced substantial immune stimulation after three doses. Even though the antibody levels, induced by our DNA vaccine, were lower than those obtained in mice immunized with dengue-4 virus the levels of protection were high with this vaccine. This observation is further supported by the fact that 80% of the vaccine immunized group was protected against lethal challenge. In conclusion, we developed a DNA vaccine employing the genes of the prM and E proteins from dengue-4 virus that protects mice against this virus.

摘要

一种表达登革热 4 型病毒前膜(prM)和包膜(E)基因的 DNA 疫苗是通过将这些基因插入哺乳动物表达质粒(pCI)中而产生的。经过彻底筛选,包括体外确认蛋白表达,选择表达这些基因的重组克隆并用于免疫 BALB/c 小鼠。经过 3 次免疫,所有动物均产生了针对登革热 4 型病毒的可检测水平的中和抗体。从免疫小鼠的脾脏中检测到的细胞因子水平和 T 细胞增殖表明,我们的构建物在 3 次剂量后引起了实质性的免疫刺激。尽管我们的 DNA 疫苗诱导的抗体水平低于用登革热 4 型病毒免疫的小鼠,但这种疫苗的保护水平很高。这一观察结果进一步得到了以下事实的支持,即 80%的疫苗免疫组免受致死性挑战的保护。总之,我们开发了一种 DNA 疫苗,该疫苗使用登革热 4 型病毒的 prM 和 E 蛋白基因,可保护小鼠免受该病毒的侵害。

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