2023-05-01 アルゴンヌ国立研究所(ANL)
◆これにより、科学者や製薬会社が、広範囲にわたって効果的なワクチンや抗ウイルス薬を開発するための可能性が生まれた。研究により、抗体はS2サブユニットにバインドし、広範な株を中和することができると判明した。
<関連情報>
- https://www.anl.gov/article/advanced-photon-source-powers-the-search-for-broadly-effective-coronavirus-antibody-treatment
- https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(22)00523-6
幹ヘリックスを標的とする希少な収束型抗体は、多様なベータコロナウイルスを広く中和する Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses
Cherrelle Dacon,Linghang Peng,Ting-Hui Lin,Courtney Tucker,Chang-Chun D. Lee,Yu Cong,Lingshu Wang,Lauren Purser,Andrew J.R. Cooper,Jazmean K. Williams,Chul-Woo Pyo,Meng Yuan,Ivan Kosik,Zhe Hu,Ming Zhao,Divya Mohan,Mary Peterson,Jeff Skinner,Saurabh Dixit,Erin Kollins,Louis Huzella,Donna Perry,Russell Byrum,Sanae Lembirik,Michael Murphy,Yi Zhang,Eun Sung Yang,Man Chen,Kwanyee Leung,Rona S. Weinberg,Amarendra Pegu,Daniel E. Geraghty,Edgar Davidson, Benjamin J. Doranz,Iyadh Douagi,Susan Moir,Jonathan W. Yewdell,Connie Schmaljohn,Peter D. Crompton,John R. Mascola,Michael R. Holbrook,David Nemazee,Ian A. Wilson,Joshua Tan
Cell Host and Microbe Published:November 07, 2022
DOI:https://doi.org/10.1016/j.chom.2022.10.010
Highlights
•Isolation of 55 broadly reactive monoclonal antibodies to betacoronaviruses
•Only a minority are broadly neutralizing and target the stem helix
•Identification of an IGHV1-46/IGKV3-20 gene signature of the broad neutralizers
•Structures of IGHV1-46/IGKV3-20 antibodies reveal a conserved mode of binding
Summary
Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5–1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.
