ジャーナル: bioRxiv / 年: 2021 タイトル: Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617. 著者: Lei Peng / Yingxia Hu / Madeleine C Mankowski / Ping Ren / Rita E Chen / Jin Wei / Min Zhao / Tongqing Li / Therese Tripler / Lupeng Ye / Ryan D Chow / Zhenhao Fang / Chunxiang Wu / Matthew B ...著者: Lei Peng / Yingxia Hu / Madeleine C Mankowski / Ping Ren / Rita E Chen / Jin Wei / Min Zhao / Tongqing Li / Therese Tripler / Lupeng Ye / Ryan D Chow / Zhenhao Fang / Chunxiang Wu / Matthew B Dong / Matthew Cook / Guilin Wang / Paul Clark / Bryce Nelson / Daryl Klein / Richard Sutton / Michael S Diamond / Craig B Wilen / Yong Xiong / Sidi Chen / 要旨: COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging ...COVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identified two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generated a bispecific antibody. Lead antibodies showed strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solved several cryo-EM structures at ∼3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and revealed distinct epitopes, binding patterns, and conformations. The lead clones also showed potent efficacy against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generated and characterized a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.
A: Spike glycoprotein E: Fab of antibody clone 2, light chain D: Fab of antibody clone 2, heavy chain L: Fab of antibody clone 2, light chain H: Fab of antibody clone 2, heavy chain C: Spike glycoprotein B: Spike glycoprotein G: Fab of antibody clone 2, light chain F: Fab of antibody clone 2, heavy chain ヘテロ分子
名称: the SARS-CoV-2 Spike trimer in complex with the Fab fragment of human neutralizing antibody clone 2 タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT
分子量
値: 0.19 MDa / 実験値: NO
由来(天然)
ID
Entity assembly-ID
生物種
Ncbi tax-ID
2
1
Severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2)
2697049
3
1
Homo sapiens (ヒト)
9606
由来(組換発現)
ID
Entity assembly-ID
生物種
Ncbi tax-ID
2
1
Mammalian expression vector pcDNA3.1-Flag (その他)
1944925
3
1
Homo sapiens (ヒト)
9606
緩衝液
pH: 8
試料
濃度: 0.3 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES