| Reference | ||
|---|---|---|
| Reference Type | Literature | IEDB_Reference:1039493 |
| Title | An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope. | |
| Authors | Zezhong Liu; Wei Xu; Zhenguo Chen; Wangjun Fu; Wuqiang Zhan; Yidan Gao; Jie Zhou; Yunjiao Zhou; Jianbo Wu; Qian Wang; Xiang Zhang; Aihua Hao; Wei Wu; Qianqian Zhang; Yaming Li; Kaiyue Fan; Ruihong Chen; Qiaochu Jiang; Christian T Mayer; Till Schoofs; Youhua Xie; Shibo Jiang; Yumei Wen; Zhenghong Yuan; Kang Wang; Lu Lu; Lei Sun; Qiao Wang | |
| Affiliations | Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences; Shanghai Institute of Infectious Disease and Biosecurity; the Fifth People's Hospital of Shanghai; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology); Institutes of Biomedical Sciences; Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan University, Shanghai, 200032, China; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA; GSK Vaccines, 1300, Wavre, Belgium; Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan University, Shanghai, 200032, China. zhyuan@shmu.edu.cn; CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. wangkangup@163.com; Biosafety Level 3 Laboratory, Shanghai Medical College, Fudan Un... | |
| Journal | Protein Cell | |
| Year | 2022 | |
| Abstract | New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes -coronavirus lineage B (-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan--CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against -CoV-B and newly emerging SARS-CoV-2 variants of concern. | |
| Curation Last Updated | 2024-10-08 21:48:20 | |
| Epitope | ||
|---|---|---|
| Epitope ID | 1625483 | IEDB_epitope:1625483 |
| Chemical Type | Discontinuous peptide | |
| Source Name | surface glycoprotein [Severe acute respiratory syndrome coronavirus 2] | |
| Source Organism | SARS-CoV2 | |
| Discontinuous Residues | F342, T345, R346, L368, S373, F374, W436, N437, N440, L441, K444, V445 | |
| Epitope Reference Details | ||
|---|---|---|
| Epitope Structure Defines | Partial Epitope | |
| Epitope Name | Epitope of Fab XG014 on SARS-CoV2 S | |
| Reference Region | F342, T345, R346, L368, S373, F374, W436, N437, N440, L441, K444, V445 | |
| Comments | The epitope residues were calculated from [PDB: 7V2A] as the antigen residues at 4Å atomic distance from the antibody. | |
| Location of Data in Reference | PDB 7V2A | |
| Immunization | ||
|---|---|---|
| Host Organism | Homo sapiens (human) | |
| Host Details | ||
|---|---|---|
| Host Geolocation | China [ID: GAZ_00002845] | |
| 1st In Vivo Process | ||
|---|---|---|
| In Vivo Process Type | Occurrence of infectious disease | |
| Disease State | COVID-19 | |
| Disease Stage | Post; | |
| 1st Immunogen | ||
|---|---|---|
| Epitope Relation | Source Organism | |
| Object Type | Organism | |
| Organism | SARS-CoV2 | |
| Immunization Comments | ||
|---|---|---|
| Immunization Comments | Antigen specific memory B cells from the PBMC of a convalescent COVID-19 patient were single cell sorted and immunoglobulin heavy and light chain variable region genes cloned into a human IgG expression vector. | |
| B Cell Assay | ||
|---|---|---|
| Qualitative Measurement | Positive | |
| Method/Technique | cross blocking | |
| Measurement of | qualitative binding | |
| Assayed Antibody | ||
|---|---|---|
| Assayed Antibody Source Material | Purified Immunoglobulin | |
| Assayed Antibody Immunoglobulin Domain | Entire Antibody | |
| Assayed Antibody Purification Status | Monoclonal | |
| Assayed Antibody Name | XG016 | |
| Assayed Antibody Heavy Chain Type | IgG | |
| Antigen | ||
|---|---|---|
| Epitope Relation | Fragment of Source Antigen | |
| Chemical Type | Linear peptide | |
| Linear Sequence | RVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNL | |
| Source Molecule Name | surface glycoprotein [Severe acute respiratory syndrome coronavirus 2] | |
| Source Organism | SARS-CoV2 | |
| Starting Position | 319 | |
| Ending Position | 533 | |
| Antigen Details | ||
|---|---|---|
| Antigen Reference Name | RBD | |
| Assay Reference Details | ||
|---|---|---|
| Assay Comments by IEDB Curator | Binding by the mAb XG016 to the RBD was inhibited by the mAb XG014 demonstrating a shared epitope. | |
| Location of Assay Data in Reference | Figure 5 | |