SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge
SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge
复制标题
DOI：
10.1101/2021.11.29.470349
复制
发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Edward Sullivan;Po-Yu Sung;Weining Wu;N. Berry;S. Kempster;D. Ferguson;N. Almond;I. Jones;P. Roy
中科院分区：
文献类型：
--
作者：
Edward Sullivan;Po-Yu Sung;Weining Wu;N. Berry;S. Kempster;D. Ferguson;N. Almond;I. Jones;P. Roy
由SARS-CoV-2感染引起的Covid-19大流行凸显了快速生产针对新出现疾病的有效疫苗的必要性。病毒样颗粒（VLP）是一种成熟的疫苗技术，它基于靶病毒结构蛋白的表达产生病毒样模拟物，可以刺激强烈的中和抗体反应。SARS-CoV-2是一种冠状病毒，其中VLP形成的基础已被证明是刺突、膜和包膜结构蛋白的共表达。在这里，我们描述了SARS-CoV-2 VLP的产生的显着的结构蛋白在昆虫细胞中的共表达，使用建立的杆状病毒表达系统。VLP是异源的直径约100 nm的包膜颗粒，具有明显的边缘，与SARS-CoV-2恢复期血清强烈反应。在叙利亚仓鼠攻击模型中，非佐剂化的VLP诱导了针对VLP相关的武汉S蛋白的中和抗体，减少了SARS-CoV-2（B.1.1.7变体）强毒攻击后的病毒脱落，并防止了疾病相关的体重减轻。与未免疫的对照组相比，免疫动物显示出减少的肺病理学和较低的攻击病毒复制。我们的数据，使用一种成熟的和可扩展的技术，表明SARS-CoV-2 VLP提供了一种有效的疫苗，可以减轻病毒负荷并预防严重疾病。
The Covid-19 pandemic caused by SARS-CoV-2 infection has highlighted the need for the rapid generation of efficient vaccines for emerging disease. Virus-like particles, VLPs, are an established vaccine technology that produces virus-like mimics, based on expression of the structural proteins of a target virus that can stimulate strong neutralizing antibody responses. SARS-CoV-2 is a coronavirus where the basis of VLP formation has been shown to be the co-expression of the spike, membrane and envelope structural proteins. Here we describe the generation of SARS-CoV-2 VLPs by the co-expression of the salient structural proteins in insect cells using the established baculovirus expression system. VLPs were heterologous ∼100nm diameter enveloped particles with a distinct fringe that reacted strongly with SARS-CoV-2 convalescent sera. In a Syrian hamster challenge model, a non-adjuvanted VLPs induced neutralizing antibodies to the VLP-associated Wuhan S protein, reduced virus shedding following a virulent challenge with SARS-CoV-2 (B.1.1.7 variant) and protected against disease associated weight loss. Immunized animals showed reduced lung pathology and lower challenge virus replication than the non-immunized controls. Our data, using an established and scalable technology, suggest SARS-CoV-2 VLPs offer an efficient vaccine that mitigates against virus load and prevents severe disease.