SARS-CoV-2のP.1株による抗体回避
Wanwisa Dejnirattisai1, Daming Zhou2, Piyada Supasa1
1Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Cell
|April 14, 2021
まとめ
P.1 と B.1.351 のような新しいSARS-CoV-2変種は,ACE2結合に影響する変異を有する. モノクローナル抗体222は,これらの変異体を中和し,その軽鎖は,それらに対する抗体の効力を回復させることができる.
科学分野:
- ウイルス学
- 免疫学
- 構造生物学
背景:
- SARS-CoV-2 パンデミックは,世界的なワクチン接種の努力を必要としています.
- 現在のワクチンは,初期のSARS-CoV-2単離体のスパイクタンパク質を標的にしています.
- 新生変種 (P.1,B.1.351,B.1.1.7) は,ACE2結合部位を含む複数のスパイク変異を有する.
研究 の 目的:
- SARS-CoV-2の変異がACE2結合親和性と中和に与える影響を調査する.
- 新興のSARS-CoV-2変種に対するモノクローナル抗体 (mAb) 222の有効性を評価する.
- mAb 222 中和の構造的基礎と抗体の効能を回復する可能性を理解する.
主な方法:
- SARS-CoV-2のスパイクタンパク質変種の構造分析.
- 変異したスパイクタンパク質に対するACE2結合親和性の評価
- 自然に感染したまたはワクチン接種した個体と単一クローン抗体からの血清を用いた中和測定法.
- mAb222とスパイクタンパク質の相互作用の構造分析
主要な成果:
- P.1 と B.1.351 の変異,特に E484K,K417N/T,および N501Y トリプレットは,ACE2 結合親和性を増加させる.
- P.1はB.1.351と比較して抗体中和に対する抵抗性が低く,非受容体結合ドメイン (RBD) 変異の影響を示しています.
- mAb222は,ACE2結合部位内の標的変異にもかかわらず,P. 1,B.1. 351,B.1. 1.7の変異を効果的に中和する.
- 構造的な洞察は,mAb 222が複数の変異体を中和し,その軽鎖が公共の抗体への中和を回復することを示しています.
結論:
- SARS-CoV-2の変異は,ACE2結合と抗体中和感性に著しく影響する.
- モノクローナル抗体222は,主要なSARS-CoV-2変種に対する広範な中和活性を示しています.
- mAb222スパイク相互作用の構造的な理解は,広範な保護性抗体治療の開発のための基礎を提供します.
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