最近のSARS-CoV-2変種における抗原漂移の構造的および機能的影響
Meng Yuan1, Deli Huang2, Chang-Chun D Lee1
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science (New York, N.Y.)
|May 21, 2021
まとめ
SARS-CoV-2のスパイクタンパク質の受容体結合部位を標的とした中和抗体は,新しい変種に対して効果が低い. E484KとK417Nのような変異は,抗体の有効性を著しく低下させ,ワクチンと治療の開発に影響を与えます.
科学分野:
- ウイルス学
- 免疫学
- 構造生物学
背景:
- 深刻な急性呼吸器症候群のコロナウイルス2型 (SARS-CoV-2) は,スパイクタンパク質の受容体結合部位 (RBS) に変異を呈する.
- これらの変異は,特に残留物Glu484,Lys417およびAsn501では,B.1.351およびP.1のような変異種に見られます.
- 野生型RBSを標的とする中和抗体 (nAbs) は,ウイルスによる免疫回避を理解するために極めて重要です.
研究 の 目的:
- 特定のSARS-CoV-2スパイクタンパク質変異 (E484K,K417N) がアンジオテンシン変換酵素2への結合に与える影響を分析する.
- これらの変異がCOVID-19患者の抗体の中和活動に与える影響を評価する.
- SARS-CoV-2 変種における抗体耐性の構造的基礎を理解する.
主な方法:
- SARS-CoV-2のスパイクタンパク質の受容体結合部位 (RBS) の変異の分析.
- アンジオテンシン変換酵素2結合親和性の評価
- COVID-19患者の抗体を用いた中和抗体結合および中和アッセイの特徴化.
- 抗体とRBSの相互作用の構造分析
主要な成果:
- 変異K417NおよびE484Kは,RBSを標的とする一般的な抗体ファミリー (IGHV3-53/3-66およびIGHV1-2) の結合および中和活性を著しく低下させる.
- 構造的な説明は,これらの変異とRBSを標的とするnAbsの間の広範な相互作用を明らかにし,廃止につながります.
- 保存されたクロス中和部位 (CR3022,S309) を標的にする抗体は,これらの変異にほとんど影響を受けなかった.
結論:
- SARS-CoV-2のスパイクタンパク質の特定の変異は,一般的な抗体ファミリーによる中和を回避することができます.
- これらの耐性メカニズムの理解は 効果的な次世代ワクチンの設計に不可欠です
- 抗体療法は,変異種特有の免疫回避を克服するために再評価または再設計する必要があるかもしれません.
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