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SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19

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收录情况： ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C

作者：
Xiaoying Ma[1,2,3] * ; Jady Liang[2,4] * ; Guangheng Zhu[2,3,5] * ; Preeti Bhoria[1,2,3,5] * ; Aron A. Shoara[2,3,4] * ; Daniel T. MacKeigan[2,3,4] ; Christopher J. Khoury[1,2,3] ; Sladjana Slavkovic[1,2,5,6] ; Lisha Lin[2,3] ; Danielle Karakas[1,2,3] ; Ziyan Chen[1,2,3,6] ; Viktor Prifti[1,2,3] ; Zhenze Liu[1,2,3] ; Chuanbin Shen[1,2,3] ; Yuchong Li[2,7] ; Cheng Zhang[5,8] ; Jiayu Dou[2,3] ; Zack Rousseau[1,2,3] ; Jiamin Zhang[1,2,3] ; Tiffany Ni[1,2,3] ; Xi Lei[2,3,5] ; Pingguo Chen[1,2,3,6] ; Xiaoyu Wu[9] ; Hamed Shaykhalishahi[2,3,5] ; Samira Mubareka[1,10] ; Kim A. Connelly[2,11,12] ; Haibo Zhang[2,7,10,13,14] ; Ori Rotstein[2,15] ; Heyu Ni[1,2,3,4,5,6,11] ;
机构： [1]Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada [2]Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science of St.Michael’sHospital, Toronto, ON, Canada [3]Toronto Platelet Immunobiology Group, Toronto, ON, Canada [4]Departmentof Physiology, University of Toronto, Toronto, ON, Canada [5]CCOA Therapeutics Inc.,Toronto, ON, Canada [6]Canadian Blood Services Centre for Innovation, Toronto, ON, Canada [7]The State Key Laboratory of RespiratoryDisease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou MedicalUniversity, Guangzhou, Guangdong, China [8]Department of Laboratory Medicine, The Second AffiliatedHospital of Guangzhou University of Chinese Medicine, Guangzhou, China [9]Advanced Pharmaceutics &Drug Delivery Laboratory, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada [10]Department of Medical Microbiology and Infectious Disease, Sunnybrook Health Science Centre, Toronto,ON, Canada [11]Department of Medicine, University of Toronto, Toronto, ON, Canada [12]Division of Cardiology,St.Michael's Hospital, Toronto, ON, Canada [13]Department of Anesthesiology and Pain Medicine and Divisionof Critical Care Medicine, University of Toronto, Toronto, ON, Canada [14]Interdepartmental Division of CriticalCare Medicine, University of Toronto, Toronto, ON, Canada [15]Department of Surgery, University of Toronto,Toronto, ON, Canada
出处：
DOI： 10.34133/research.0124
ISSN：

摘要：
The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health burden. Severe cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia (VITT) are both associated with thrombosis and thrombocytopenia; however, the underlying mechanisms remain inadequately understood. Both infection and vaccination utilize the spike protein receptor-binding domain (RBD) of SARS-CoV-2. We found that intravenous injection of recombinant RBD caused significant platelet clearance in mice. Further investigation revealed the RBD could bind platelets, cause platelet activation, and potentiate platelet aggregation, which was exacerbated in the Delta and Kappa variants. The RBD-platelet interaction was partially dependent on the β3 integrin as binding was significantly reduced in β3-/- mice. Furthermore, RBD binding to human and mouse platelets was significantly reduced with related αIIbβ3 antagonists and mutation of the RGD (arginine-glycine-aspartate) integrin binding motif to RGE (arginine-glycine-glutamate). We developed anti-RBD polyclonal and several monoclonal antibodies (mAbs) and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation, aggregation, and clearance in vivo, and SARS-CoV-2 infection and replication in Vero E6 cells. Our data show that the RBD can bind platelets partially though αIIbβ3 and induce platelet activation and clearance, which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and VITT. Our newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.Copyright © 2023 Xiaoying Ma et al.

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出版当年[2022]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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出版当年[2021]版：
Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada [2]Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science of St.Michael’sHospital, Toronto, ON, Canada [3]Toronto Platelet Immunobiology Group, Toronto, ON, Canada
共同第一作者：
通讯作者：
通讯机构： [1]Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada [2]Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science of St.Michael’sHospital, Toronto, ON, Canada [3]Toronto Platelet Immunobiology Group, Toronto, ON, Canada [4]Departmentof Physiology, University of Toronto, Toronto, ON, Canada [5]CCOA Therapeutics Inc.,Toronto, ON, Canada [6]Canadian Blood Services Centre for Innovation, Toronto, ON, Canada [11]Department of Medicine, University of Toronto, Toronto, ON, Canada
推荐引用方式(GB/T 7714)：
Xiaoying Ma,Jady Liang,Guangheng Zhu,et al.SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19[J].RESEARCH.2023,6:doi:10.34133/research.0124.
APA：
Xiaoying Ma,Jady Liang,Guangheng Zhu,Preeti Bhoria,Aron A. Shoara...&Heyu Ni.(2023).SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19.RESEARCH,6,
MLA：
Xiaoying Ma,et al."SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance: Implications for Antibody Therapy and Vaccinations against COVID-19".RESEARCH 6.(2023)

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