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登革 2 型病毒核衣壳样颗粒增强了对登革 4 型病毒重组蛋白的免疫应答。

Nucleocapsid-like particles of dengue-2 virus enhance the immune response against a recombinant protein of dengue-4 virus.

机构信息

Vaccine Division, Center for Genetic Engineering and Biotechnology (CIGB), Havana 6, Cuba.

出版信息

Arch Virol. 2010 Oct;155(10):1587-95. doi: 10.1007/s00705-010-0734-9. Epub 2010 Jul 18.

Abstract

In this study, we evaluate in mice a novel formulation containing nucleocapsid-like particles of dengue-2 virus (recNLP) co-immunized with a chimeric protein composed of the dengue-4 envelope domain III fused twice within the meningococcal P64k protein of Neisseria meningitidis (PD24). The animals receiving the PD24-recNLP mixture showed the highest levels of antiviral antibodies. Similar results were obtained for IFNγ secretion levels, indicating a functional Th1 cellular response. Consistently, the percentage of mice surviving after viral challenge was significantly higher for those immunized with the mixture than for those inoculated with PD24 protein alone. In addition, in vivo depletion experiments demonstrated the decisive role of CD4(+) and CD8(+) cells in the protection conferred by immunization with PD24-recNLP. In conclusion, this report demonstrates for the first time the adjuvant capacity of dengue-2 virus recNLP. Additionally, the evidence presented highlights the potential of these particles for enhancing the immune response against heterologous recombinant proteins.

摘要

在这项研究中,我们在小鼠中评估了一种新型制剂,该制剂包含登革热 2 型病毒的核衣壳样颗粒(recNLP),与由两次融合在脑膜炎奈瑟球菌 P64k 蛋白内的登革 4 型包膜结构域 III 组成的嵌合蛋白(PD24)共同免疫。接受 PD24-recNLP 混合物的动物显示出最高水平的抗病毒抗体。IFNγ 分泌水平的相似结果表明存在功能性 Th1 细胞反应。一致地,与单独接种 PD24 蛋白的小鼠相比,用混合物免疫的小鼠在病毒攻击后存活的百分比显著更高。此外,体内耗竭实验证明了 CD4(+)和 CD8(+)细胞在 PD24-recNLP 免疫赋予的保护中的决定性作用。总之,本报告首次证明了登革热 2 型病毒 recNLP 的佐剂能力。此外,所提出的证据强调了这些颗粒增强针对异源重组蛋白的免疫反应的潜力。

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