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TitleBroadly neutralizing antibodies derived from the earliest COVID-19 convalescents protect mice from SARS-CoV-2 variants challenge.
Journal, issue, pagesSignal Transduct Target Ther, Vol. 8, Issue 1, Page 347, Year 2023
Publish dateSep 14, 2023
AuthorsQianyun Liu / Haiyan Zhao / Zhiqiang Li / Zhen Zhang / Rui Huang / Mengxue Gu / Ke Zhuang / Qing Xiong / Xianying Chen / Weiyi Yu / Shengnan Qian / Yuzhen Zhang / Xue Tan / Muyi Zhang / Feiyang Yu / Ming Guo / Zhixiang Huang / Xin Wang / Wenjie Xiang / Bihao Wu / Fanghua Mei / Kun Cai / Limin Zhou / Li Zhou / Ying Wu / Huan Yan / Sheng Cao / Ke Lan / Yu Chen /
PubMed AbstractCoronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we ...Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.5. Of these mAbs, the two most broadly and potently neutralizing mAbs (7B3 and 14B1) exhibit prophylactic activity against SARS-CoV-2 WT infection and therapeutic effects against SARS-CoV-2 Delta variant challenge in K18-hACE2 KI mice. Furthermore, post-exposure treatment with 7B3 protects mice from lethal Omicron variants infection. Cryo-EM analysis of the spike trimer complexed with 14B1 or 7B3 reveals that these two mAbs bind partially overlapped epitopes onto the RBD of the spike, and sterically disrupt the binding of human angiotensin-converting enzyme 2 (hACE2) to RBD. Our results suggest that mAbs with broadly neutralizing activity against different SARS-CoV-2 variants are present in COVID-19 convalescents infected by the ancestral SARS-CoV-2 strain, indicating that people can benefit from former infections or vaccines despite the extensive immune escape of SARS-CoV-2.
External linksSignal Transduct Target Ther / PubMed:37704615 / PubMed Central
MethodsEM (single particle)
Resolution3.6 - 3.9 Å
Structure data

35155

8i3s

EMDB-35155, PDB-8i3s:
Local CryoEM structure of the SARS-CoV-2 S6P in complex with 7B3 Fab
Method: EM (single particle) / Resolution: 3.9 Å

35156

8i3u

EMDB-35156, PDB-8i3u:
Local CryoEM structure of the SARS-CoV-2 S6P in complex with 14B1 Fab
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-Cov-2 / receptor binding domain / RBD / Fab / coronavirus / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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