SARS-CoV-2変種とSARS-CoVのクロスニュートラライゼーションの背後にあるB細胞ゲノミクス
Johannes F Scheid1, Christopher O Barnes2, Basak Eraslan3
1Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Cell
|May 20, 2021
まとめ
研究者は,SARS-CoV-2に対するB細胞の反応を特徴づけ,強力な中和抗体 (nAbs) を生成する異なる集団を特定した. これらのnAbsは保存されたエピトープを標的とし,コロナウイルスに対する広範な保護を提供し,将来のワクチンおよび治療設計に情報を提供する.
科学分野:
- 免疫学
- ウイルス学
- 構造生物学
背景:
- モノクローナル抗体 (mAbs) は,SARS-CoV-2およびその変種との闘いにおいて極めて重要です.
- B細胞の反応を理解することは 効果的なワクチンや治療薬の設計の鍵です
研究 の 目的:
- 統合された単細胞技術を用いて,SARS-CoV-2に対するB細胞の反応を特徴づける.
- 強力な中和抗体 (nAbs) とその治療開発の標的を特定する.
主な方法:
- 単細胞VDJとRNAシーケンシング (RNA-seq) を併用したB細胞分類
- 凍結電子顕微鏡を用いて,SARS-CoV-2のスパイクトリマーと複合したnAbsの構造を決定した.
主要な成果:
- 記憶と活性化されたB細胞に似ているnAbsを生成するB細胞を含む,転写的に異なるB細胞集団を特定した.
- 構造分析により,nAbsは様々な受容体結合領域 (RBD) エピトープを標的としていることが明らかになった.
- 1 mAb,BG10-19は,SARS-CoV-2,変種 (B.1.1.7,B.1.351),およびSARS-CoVを閉じた形状でスパイクトリマーをロックすることによって中和する.
結論:
- SARS-CoV-2に特異的なB細胞内のトランスクリプションの異質性.
- より広範なコロナウイルス保護のためのクロス中和抗体の標的を発見した.
- この発見は,次世代の免疫因子とコロナウイルスに対する治療薬の設計を導きます.
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