Enterovirus 71 (EV71) belonging to the Picornaviridae family is considered the most frequently detected causative agent in hand-foot-and-mouth disease (HFMD) and is a serious threat to public health in the Asia-Pacific region. There are currently no approved vaccines or effective drugs for EV71. In this study, using recombinant vesicular stomatitis virus (rVSV) expressing viral VP1 protein (mVP1) of EV71 as a control, we generated two types of rVSVs that can form EV71 virus-like particles (VLPs). First, we co-infected two rVSVs singly expressing P1 (mP1) and 3CD (m3CD) of EV71. Second, we inserted P1 and 3CD into one VSV backbone to generate an rVSV expressing P1 and 3CD together (mP1-3CD). When P1 and 3CD were expressed in the cells either co-infected with mP1 and m3CD (mP1/m3CD) or infected with mP1-3CD, P1 was cleaved by 3CD and produced VP1, VP3, and VP0 to form VLPs. Furthermore, mice immunized with mP1/m3CD or mP1-3CD showed higher humoral and cellular immunity responses than mice immunized with mVP1. Finally, the rVSVs expressing the EV71 proteins were evaluated in mice to determine their potential to protect against a lethal EV71 virus challenge, and among all the rVSVs, the mP1-3CD was shown to be the most promising vaccine candidate for EV71 protection.

中文翻译：

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表达EV71病毒样颗粒的基于水泡性口炎病毒的疫苗引起强烈的免疫反应，并保护新生小鼠免受致命性攻击。

属于Picornaviridae家族的肠道病毒71（EV71）被认为是手足口病（HFMD）中最常见的病原体，对亚太地区的公共健康构成了严重威胁。目前尚无批准用于EV71的疫苗或有效药物。在这项研究中，使用表达EV71病毒VP1蛋白（mVP1）的重组水泡性口腔炎病毒（rVSV）作为对照，我们生成了两种类型的rVSV，它们可以形成EV71病毒样颗粒（VLP）。首先，我们共同感染了两个分别表达EV71的P1（mP1）和3CD（m3CD）的rVSV。其次，我们将P1和3CD插入一个VSV主干中，以生成一个同时表达P1和3CD的rVSV（mP1-3CD）。当在同时感染mP1和m3CD（mP1 / m3CD）或感染mP1-3CD的细胞中表达P1和3CD时，P1被3CD裂解并产生VP1，VP3和VP0组成VLP。此外，用mP1 / m3CD或mP1-3CD免疫的小鼠比用mVP1免疫的小鼠表现出更高的体液和细胞免疫应答。最后，在小鼠中评估了表达EV71蛋白的rVSV，以确定其对致命EV71病毒攻击的保护能力，在所有rVSV中，mP1-3CD被证明是最有希望保护EV71的疫苗。