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单纯疱疹病毒 1 型突变体能导致减毒表型,并具有保护作用的免疫诱导效果。

A HSV1 mutant leads to an attenuated phenotype and induces immunity with a protective effect.

机构信息

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, China.

Weirui Biotechnology (Kunming) Co., Ltd, Kunming, China.

出版信息

PLoS Pathog. 2020 Aug 10;16(8):e1008703. doi: 10.1371/journal.ppat.1008703. eCollection 2020 Aug.

Abstract

Herpes simplex virus type 1 (HSV1) is a complicated structural agent with a sophisticated transcription process and a high infection rate. A vaccine against HSV1 is urgently needed. As multiple viral-encoded proteins, including structural and nonstructural proteins, contribute to immune response stimulation, an attenuated or deficient HSV1 vaccine may be relatively reliable. Advances in genomic modification technologies provide reliable means of constructing various HSV vaccine candidates. Based on our previous work, an M6 mutant with mutations in the UL7, UL41, LAT, Us3, Us11 and Us12 genes was established. The mutant exhibited low proliferation in cells and an attenuated phenotype in an animal model. Furthermore, in mice and rhesus monkeys, the mutant can induce remarkable serum neutralizing antibody titers and T cell activation and protect against HSV1 challenge by impeding viral replication, dissemination and pathogenesis.

摘要

单纯疱疹病毒 1 型(HSV1)是一种结构复杂的病原体,具有复杂的转录过程和较高的感染率。因此,迫切需要开发针对 HSV1 的疫苗。HSV1 编码多种病毒蛋白,包括结构蛋白和非结构蛋白,这些蛋白均可刺激机体的免疫反应。因此,减毒或缺失的 HSV1 疫苗可能相对可靠。基因组修饰技术的进步为构建各种 HSV 疫苗候选物提供了可靠的手段。基于我们之前的工作,构建了 UL7、UL41、LAT、Us3、Us11 和 Us12 基因突变的 M6 突变体。该突变体在细胞中增殖能力较低,在动物模型中表现出减毒表型。此外,在小鼠和恒河猴中,该突变体能诱导显著的血清中和抗体滴度和 T 细胞激活,并通过抑制病毒复制、传播和发病机制来保护机体免受 HSV1 攻击。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a327/7440667/08e734dbb211/ppat.1008703.g001.jpg

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