SARS-CoV-2 Virus-like Particles Produced by a Single Recombinant Baculovirus Generate Anti-S Antibody and Protect against Variant Challenge.

SARS-CoV-2 Virus-like Particles Produced by a Single Recombinant Baculovirus Generate Anti-S Antibody and Protect against Variant Challenge.
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DOI:
10.3390/v14050914
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发表时间:
2022-04-27
期刊:
Viruses
影响因子:
--
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--
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其他
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由严重急性呼吸道综合征冠状病毒2型(SARS-CoV-2)感染引起的2019年冠状病毒病(COVID-19)凸显了快速生产新型疾病有效疫苗的需求。病毒样颗粒(VLP)是一种成熟的疫苗技术,其基于靶病毒的结构蛋白的表达产生病毒样模拟物。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是直径约100 nm的异源包膜颗粒,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VLP诱导针对VLP相关武汉S蛋白的中和抗体,并减少病毒脱落,并在SARS-CoV-2(B.1.1.7变体)强毒攻击后防止疾病相关体重减轻。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。
Coronavirus Disease 2019 (COVID-19), caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), 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. 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 ~100 nm diameter enveloped particles with a distinct fringe that reacted strongly with SARS-CoV-2 convalescent sera. In a Syrian hamster challenge model, non-adjuvanted VLPs induced neutralizing antibodies to the VLP-associated Wuhan S protein and reduced virus shedding and protected against disease associated weight loss following a virulent challenge with SARS-CoV-2 (B.1.1.7 variant). Immunized animals showed reduced lung pathology and lower challenge virus replication than the non-immunized controls. Our data suggest SARS-CoV-2 VLPs offer an efficient vaccine that mitigates against virus load and prevents severe disease.
DOI: 10.1038/s41586-020-2852-1
发表时间: 2020-12
期刊: Nature
影响因子: 64.8
作者:
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
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DOI: 10.1126/science.abg3055
发表时间: 2021-04-09
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
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DOI: 10.3389/fgeed.2020.579297
发表时间: 2020
影响因子: --
作者:
Lundstrom K
通讯作者: Lundstrom K
DOI: 10.1038/s41586-020-2665-2
发表时间: 2020-08-17
期刊: NATURE
影响因子: 64.8
作者:
Ke, Zunlong;Oton, Joaquin;Briggs, John A. G.
通讯作者: Briggs, John A. G.
DOI: 10.3390/v12091054
发表时间: 2020-09-22
期刊: Viruses
影响因子: --
作者:
Alsaadi EAJ;Neuman BW;Jones IM
通讯作者: Jones IM