懸念されるB.1.427/B.1.429変種によるSARS-CoV-2免疫回避
Matthew McCallum1, Jessica Bassi2, Anna De Marco2
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Science (New York, N.Y.)
|July 2, 2021
まとめ
新しいSARS-CoV-2変種であるCAL.20C (B.1.427/B.1.429) は,ワクチンおよび過去の感染による中和が減少していることを示しています. スパイクタンパク質の重要な変異は N端領域を改造し 抗体反応を回避します
科学分野:
- ウイルス学
- 免疫学
- 構造生物学
背景:
- 懸念される新型SARS-CoV-2変種CAL.20C (B.1.427/B.1.429) は,特定の変異を伴って出現した.
- これらの変異は,信号ペプチドのS13I,N端領域 (NTD) のW152C,受容体結合領域 (RBD) のL452Rを含む.
研究 の 目的:
- CAL.20C変異が抗体による中和に与える影響を調査する.
- 抗体回避の構造的根拠を理解するために
主な方法:
- ワクチンを接種した患者および回復中の患者からの血を用いた中和測定法.
- 特定の変異に対するモノクローナル抗体の活性度の評価
- スパイクタンパク質の変化を分析するための質量スペクトロメトリーと構造研究.
主要な成果:
- CAL. 20Cに対する中和位数は,野生型と比較して2倍から3. 5倍減少した.
- L452R変異は,34のRBD特異のモノクローナル抗体による中和を阻害した.
- S13IとW152Cの変異は10のNTD特異のモノクローナル抗体の中和を完全に失いました.
- 構造分析により NTDの抗原スーパーサイトが 改造されていることが判明しました
結論:
- CAL.20Cの変種は,そのスパイクタンパク質の変異により,有意な免疫回避を示しています.
- 変異はNTDを改造し,特定の抗体による中和が完全に失われる.
- これらの発見は,SARS-CoV-2の変種が進化する脅威と,更新されたワクチンまたは治療法の必要性を強調しています.
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