Semisynthesis of homogeneous spike RBD glycoforms from SARS-CoV-2 for profiling the correlations between glycan composition and function

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外文摘要：Vaccines have been the primary remedy in the global fight against coronavirus disease 2019(COVID-19).The receptor-binding domain(RBD)of the spike protein,a critical viral immunogen,is affected by the heterogeneity of its glycan structures and relatively low immunogenicity.Here,we describe a scalable synthetic platform that enables the precise synthesis of homogeneously glycosylated RBD,facilitating the elucidation of carbohydrate structure-function relationships.Five homogeneously glycosylated RBDs bearing biantennary glycans were prepared,three of which were conjugated to T-helper epitope(Tpep)from tetanus toxoid to improve their weak immune response.Relative to natural HEK293-derived RBD,synthetic RBDs with biantennary N-glycan elicited a higher level of neutralising antibodies against SARS-CoV-2 in mice.Furthermore,RBDs containing Tpep elicited significant immune responses in transgenic mice expressing human angiotensin-converting enzyme 2.Our collective data suggest that trimming the N-glycans and Tpep conjugation of RBD could potentially serve as an effective strategy for developing subunit vaccines providing efficient protection.

外文关键词：

peptide ligationglycosylationglycoprotein

作者：

Farong Ye、Cheng Li、Feng-Liang Liu、Xinliang Liu、Peng Xu、Rong-Hua Luo、Wenping Song、Yong-Tang Zheng、Tianlei Ying、Biao Yu、Ping Wang

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作者单位：

Center for Chemical Glycobiology,Frontiers Science Center for Transformative Molecules,Zhangjiang Institute for Advanced Study,School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China

MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology,Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection,Shanghai Institute of Infectious Disease and Biosecurity,Shanghai Engineering Research Center for Synthetic Immunology,School of Basic Medical Sciences,Shanghai Medical College,Fudan University,Shanghai 200032,China

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province,Center for Biosafety Mega-Science,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China

State Key Laboratory of Bioorganic and Natural Products Chemistry,Center for Excellence in Molecular Synthesis,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032,China

Shenzhen Research Institute of Shanghai Jiao Tong University,Shenzhen 518057,China

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基金：

National Science Fund for Distinguished Young ScholarsNational Natural science Foundation of ChinaNational Natural science Foundation of ChinaNational Natural science Foundation of ChinaShanghai Pilot Program for Basic Research-Shanghai Jiao Tong UniversityNational Key R & D Program of ChinaNational Key R & D Program of ChinaSpecial Projects of the Central Government in Guidance of Local Science and Technology Development

项目编号：

2222570192253302220770803197087921TQ14002102021YFC23013032022YFC23037002021Szvup077

出版年：

2024

DOI：

10.1093/nsr/nwae030

国家科学评论(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.11(2)

参考文献量49