The synergistic effect of combined immunization with a DNA vaccine and chimeric yellow fever/dengue virus leads to strong protection against dengue.

The synergistic effect of combined immunization with a DNA vaccine and chimeric yellow fever/dengue virus leads to strong protection against dengue.
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DOI:
10.1371/journal.pone.0058357
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Alves AM
Alves AM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Azevedo AS;Gonçalves AJ;Archer M;Freire MS;Galler R;Alves AM

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登革病毒包膜糖蛋白(E)是病毒粒子表面的主要成分,其胞外域由结构域I、II和III组成。这种蛋白质是开发具有诱导中和抗体的登革热疫苗的主要靶标。在目前的工作中,我们测试了两种不同的疫苗接种策略,在初免/加强免疫方案或同时接种DNA疫苗(pE 1D 2)和嵌合黄热病/登革热2型病毒(YF 17 D-D2)的联合免疫。pE 1D 2 DNA疫苗编码与t-PA信号肽融合的包膜DENV 2蛋白的胞外域,而YF 17 D-D2通过用来自DENV 2的prM和E基因替换来自17 D黄热疫苗病毒的prM和E基因来构建。Balb/c小鼠接种这两种疫苗,通过不同的初免/加强或同时免疫方案,其中大多数诱导的免疫应答的协同效应,主要是在中和抗体的产生。此外,与单独施用的每种疫苗相比,联合免疫显著增加了针对致死剂量的DENV 2的保护。结果还显示,用DNA疫苗免疫,无论与嵌合病毒的组合如何,都诱导了强有力的细胞免疫应答,通过CD 8 + T淋巴细胞产生IFN-γ。
The dengue envelope glycoprotein (E) is the major component of virion surface and its ectodomain is composed of domains I, II and III. This protein is the main target for the development of a dengue vaccine with induction of neutralizing antibodies. In the present work, we tested two different vaccination strategies, with combined immunizations in a prime/booster regimen or simultaneous inoculation with a DNA vaccine (pE1D2) and a chimeric yellow fever/dengue 2 virus (YF17D-D2). The pE1D2 DNA vaccine encodes the ectodomain of the envelope DENV2 protein fused to t-PA signal peptide, while the YF17D-D2 was constructed by replacing the prM and E genes from the 17D yellow fever vaccine virus by those from DENV2. Balb/c mice were inoculated with these two vaccines by different prime/booster or simultaneous immunization protocols and most of them induced a synergistic effect on the elicited immune response, mainly in neutralizing antibody production. Furthermore, combined immunization remarkably increased protection against a lethal dose of DENV2, when compared to each vaccine administered alone. Results also revealed that immunization with the DNA vaccine, regardless of the combination with the chimeric virus, induced a robust cell immune response, with production of IFN-γ by CD8+ T lymphocytes.
DOI: 10.1371/journal.pone.0020528
发表时间: 2011-07-11
期刊: PLOS ONE
影响因子: 3.7
作者:
Azevedo, Adriana S.;Yamamura, Anna M. Y.;Alves, Ada M. B.
通讯作者: Alves, Ada M. B.
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期刊: VACCINE
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期刊: VACCINE
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