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多价颗粒展示受体结合域诱导针对 MERS-CoV 的保护性免疫应答。

Particulate multivalent presentation of the receptor binding domain induces protective immune responses against MERS-CoV.

机构信息

Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands.

Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

出版信息

Emerg Microbes Infect. 2020 Dec;9(1):1080-1091. doi: 10.1080/22221751.2020.1760735.

DOI:10.1080/22221751.2020.1760735
PMID:32471334
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7448924/
Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a WHO priority pathogen for which vaccines are urgently needed. Using an immune-focusing approach, we created self-assembling particles multivalently displaying critical regions of the MERS-CoV spike protein ─fusion peptide, heptad repeat 2, and receptor binding domain (RBD) ─ and tested their immunogenicity and protective capacity in rabbits. Using a "plug-and-display" SpyTag/SpyCatcher system, we coupled RBD to lumazine synthase (LS) particles producing multimeric RBD-presenting particles (RBD-LS). RBD-LS vaccination induced antibody responses of high magnitude and quality (avidity, MERS-CoV neutralizing capacity, and mucosal immunity) with cross-clade neutralization. The antibody responses were associated with blocking viral replication and upper and lower respiratory tract protection against MERS-CoV infection in rabbits. This arrayed multivalent presentation of the viral RBD using the antigen-SpyTag/LS-SpyCatcher is a promising MERS-CoV vaccine candidate and this platform may be applied for the rapid development of vaccines against other emerging viruses such as SARS-CoV-2.

摘要

中东呼吸综合征冠状病毒（MERS-CoV）是世卫组织优先病原体，急需疫苗。我们采用免疫聚焦方法，构建了多价自组装颗粒，展示了 MERS-CoV 刺突蛋白的关键区域 - 融合肽、七肽重复 2 和受体结合域（RBD），并在兔子中测试了它们的免疫原性和保护能力。我们使用“插件和显示”SpyTag/SpyCatcher 系统将 RBD 与荧光素酶（LS）颗粒偶联，产生多聚体 RBD 呈现颗粒（RBD-LS）。RBD-LS 疫苗接种诱导了高幅度和高质量的抗体反应（亲合力、MERS-CoV 中和能力和黏膜免疫），具有跨谱系中和作用。抗体反应与阻断病毒复制以及针对 MERS-CoV 感染的上呼吸道和下呼吸道保护有关。这种使用抗原-SpyTag/LS-SpyCatcher 的病毒 RBD 排列多价呈现是一种有前途的 MERS-CoV 疫苗候选物，该平台可用于快速开发针对 SARS-CoV-2 等其他新兴病毒的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/05792121c410/TEMI_A_1760735_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/7e88b6bd1c0a/TEMI_A_1760735_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/bc08c5792a70/TEMI_A_1760735_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/34ebeeba461c/TEMI_A_1760735_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/4fa3714c1202/TEMI_A_1760735_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/f178014d4747/TEMI_A_1760735_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/05792121c410/TEMI_A_1760735_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/7e88b6bd1c0a/TEMI_A_1760735_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/bc08c5792a70/TEMI_A_1760735_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/34ebeeba461c/TEMI_A_1760735_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/4fa3714c1202/TEMI_A_1760735_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/f178014d4747/TEMI_A_1760735_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/367e/7448924/05792121c410/TEMI_A_1760735_F0006_OC.jpg

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