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通过突变一个独特的抗原域的突变,形成具有低交叉反应性的flavivirus亚病毒颗粒

Koshiro Tabata^1,2, Yukari Itakura^1,2, Takuma Ariizumi¹

¹Division of Molecular Pathobiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, 001-0020, Japan.

Applied microbiology and biotechnology

|October 13, 2023

概括

研究人员修改了一个关键的病毒蛋白质域,以改善蚊子传播的黄病毒病毒 (MBFV) 的血清诊断. 这项创新降低了交叉反应性,使得能够更准确地检测特定的黄病毒感染和抗体.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
医学诊断医学诊断医学诊断

背景情况:

弗拉维病毒包膜蛋白的融合循环 (FL) 域是一个保存的表位,导致交叉反应性抗体.
这种交叉反应性使蚊子传播的病毒 (MBFV) 感染和疫苗反应的准确血清诊断复杂化.

研究的目的:

设计修改的融合环域,以克服MBFV血清诊断中的交叉反应.
开发更准确的诊断工具,以区分不同的黄病毒感染.

主要方法:

修改了保存的FL域,使用来自I系昆虫特异性黄病毒 (ISFV) 的氨基酸.
将这些突变引入了2型登革热病毒 (DENV2),寨卡病毒 (ZIKV),日本脑炎病毒 (JEV) 和西尼罗河病毒 (WNV) 的亚病毒颗粒 (SVP).
使用间接酶链免疫吸收试验 (ELISA) 和小鼠免疫模型评估抗原性和抗体结合.

主要成果:

突变的SVP显示小鼠中ZIKV,JEV和WNV感染诱导的交叉反应IgG和总Ig的结合减少.
修改后的抗原使得病毒特异性抗体的敏感检测成为可能.
与野生型SVP相比,用突变的SVP免疫接种产生了与异质MBFV抗原交叉反应性明显较低的抗体.

结论:

将I系ISFV衍生的突变引入MBFV SVP的FL域,有效地降低了交叉反应性.
这一策略显著提高了对MBFV感染的基于ELISA的间接血清诊断的准确性.
突变的SVP作为改善的抗原用于血清学测试和疫苗开发.

关键词:

交叉反应性交叉反应性融合循环领域是一个领域.特定于昆虫的黄斑病毒.蚊子传播的黄斑病毒是蚊子传播的黄斑病毒.血清诊断是一种血清诊断.亚病毒粒子亚病毒粒子

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