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-Structure paper
タイトル | Bivalent intra-spike binding provides durability against emergent Omicron lineages: Results from a global consortium. |
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ジャーナル・号・ページ | Cell Rep, Vol. 42, Issue 1, Page 112014, Year 2023 |
掲載日 | 2023年1月31日 |
著者 | Heather M Callaway / Kathryn M Hastie / Sharon L Schendel / Haoyang Li / Xiaoying Yu / Jeremy Shek / Tierra Buck / Sean Hui / Dan Bedinger / Camille Troup / S Moses Dennison / Kan Li / Michael D Alpert / Charles C Bailey / Sharon Benzeno / Jody L Bonnevier / Jin-Qiu Chen / Charm Chen / Hyeseon Cho / Peter D Crompton / Vincent Dussupt / Kevin C Entzminger / Yassine Ezzyat / Jonathan K Fleming / Nick Geukens / Amy E Gilbert / Yongjun Guan / Xiaojian Han / Christopher J Harvey / Julia M Hatler / Bryan Howie / Chao Hu / Ailong Huang / Maya Imbrechts / Aishun Jin / Nik Kamachi / Gladys Keitany / Mark Klinger / Jay K Kolls / Shelly J Krebs / Tingting Li / Feiyan Luo / Toshiaki Maruyama / Michael A Meehl / Letzibeth Mendez-Rivera / Andrea Musa / C J Okumura / Benjamin E R Rubin / Aaron K Sato / Meiying Shen / Anirudh Singh / Shuyi Song / Joshua Tan / Jeffrey M Trimarchi / Dhruvkumar P Upadhyay / Yingming Wang / Lei Yu / Tom Z Yuan / Erik Yusko / Bjoern Peters / Georgia Tomaras / Erica Ollmann Saphire / |
PubMed 要旨 | The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, ...The SARS-CoV-2 Omicron variant of concern (VoC) and its sublineages contain 31-36 mutations in spike and escape neutralization by most therapeutic antibodies. In a pseudovirus neutralization assay, 66 of the nearly 400 candidate therapeutics in the Coronavirus Immunotherapeutic Consortium (CoVIC) panel neutralize Omicron and multiple Omicron sublineages. Among natural immunoglobulin Gs (IgGs), especially those in the receptor-binding domain (RBD)-2 epitope community, nearly all Omicron neutralizers recognize spike bivalently, with both antigen-binding fragments (Fabs) simultaneously engaging adjacent RBDs on the same spike. Most IgGs that do not neutralize Omicron bind either entirely monovalently or have some (22%-50%) monovalent occupancy. Cleavage of bivalent-binding IgGs to Fabs abolishes neutralization and binding affinity, with disproportionate loss of activity against Omicron pseudovirus and spike. These results suggest that VoC-resistant antibodies overcome mutagenic substitution via avidity. Hence, vaccine strategies targeting future SARS-CoV-2 variants should consider epitope display with spacing and organization identical to trimeric spike. |
リンク | Cell Rep / PubMed:36681898 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 16.0 - 26.0 Å |
構造データ | EMDB-28090: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-040 EMDB-28091: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-045 EMDB-28092: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-093 EMDB-28093: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-156 EMDB-28094: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-234 EMDB-28095: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-260 EMDB-28096: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-279 EMDB-28097: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-290 EMDB-28098: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-294 EMDB-28099: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-295 EMDB-28100: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-299 EMDB-28102: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-334 EMDB-28103: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-360 EMDB-28104: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-361 EMDB-28105: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-362 EMDB-28106: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-368 EMDB-28168: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-292 EMDB-28169: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-333 EMDB-28170: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-355 EMDB-28171: Negative stain EM map of SARS-CoV-2 Spike in complex with CoVIC-371 |
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