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一种针对 GII.4 型人类诺如病毒 VP1 的 DNA 疫苗可诱导产生阻断抗体和 T 细胞应答。

A DNA vaccine against GII.4 human norovirus VP1 induces blocking antibody production and T cell responses.

机构信息

Department of Life Science, Gachon University, Seongnam-Si, South Korea.

Department of BioNano Technology, Gachon University, Seongnam-Si, South Korea.

出版信息

Vaccine. 2024 Feb 27;42(6):1392-1400. doi: 10.1016/j.vaccine.2024.01.090. Epub 2024 Feb 5.

Abstract

Human noroviruses (HuNoVs) are highly contagious and a leading cause of epidemics of acute gastroenteritis worldwide. Among the various HuNoV genotypes, GII.4 is the most prevalent cause of outbreaks. However, no vaccines have been approved for HuNoVs to date. DNA vaccines are proposed to serve as an ideal platform against HuNoV since they can be easily produced and customized to express target proteins. In this study, we constructed a CMV/R vector expressing a major structural protein, VP1, of GII.4 HuNoV (CMV/R-GII.4 HuNoV VP1). Transfection of CMV/R-GII.4 HuNoV VP1 into human embryonic kidney 293T (HEK293T) cells resulted in successful expression of VP1 proteins in vitro. Intramuscular or intradermal immunization of mice with the CMV/R-GII.4 HuNoV VP1 construct elicited the production of blocking antibodies and activation of T cell responses against GII.4 HuNoV VP1. Our collective data support the utility of CMV/R-GII.4 HuNoV VP1 as a promising DNA vaccine candidate against GII.4 HuNoV.

摘要

人类诺如病毒(HuNoVs)具有高度传染性,是全球急性胃肠炎暴发的主要原因。在各种 HuNoV 基因型中,GII.4 是暴发的最主要原因。然而,迄今为止,尚无针对 HuNoVs 的疫苗获得批准。由于 DNA 疫苗易于生产并且可以定制以表达目标蛋白,因此被提议作为针对 HuNoV 的理想平台。在这项研究中,我们构建了一种表达 GII.4 型 HuNoV 主要结构蛋白 VP1 的 CMV/R 载体(CMV/R-GII.4 HuNoV VP1)。CMV/R-GII.4 HuNoV VP1 转染人胚肾 293T(HEK293T)细胞后,可在体外成功表达 VP1 蛋白。用 CMV/R-GII.4 HuNoV VP1 构建物肌肉内或皮内免疫小鼠可诱导针对 GII.4 HuNoV VP1 的阻断抗体产生和 T 细胞反应的激活。我们的综合数据支持 CMV/R-GII.4 HuNoV VP1 作为针对 GII.4 HuNoV 的有前途的 DNA 疫苗候选物的效用。

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