超強力なヒトの抗体は,複数のメカニズムを通じてSARS-CoV-2に抵抗する
M Alejandra Tortorici1,2, Martina Beltramello3, Florian A Lempp4
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Science (New York, N.Y.)
|September 25, 2020
まとめ
重度の急性呼吸器症候群コロナウイルス2 (SARS-CoV-2) と戦うために,S2E12とS2M11という強力な中和抗体が特定されました. これらの抗体はハムスターを保護し,SARS-CoV-2感染を予防および治療する抗体カクテルの有望性を示しています.
科学分野:
- ウイルス学
- 免疫学
- 構造生物学
背景:
- 重症急性呼吸器症候群コロナウイルス2型 (SARS-CoV-2型) によって引き起こされる世界的なパンデミックは,効果的な治療戦略の開発を必要としています.
- 既存の治療法は,ウイルスの拡散を制御し,死亡率を軽減するために強化する必要があります.
研究 の 目的:
- SARS-CoV-2に対する新しいヒト中和抗体を分離し,特徴づけること.
- これらの抗体の治療的可能性を臨床前モデルで評価する.
- これらの抗体の作用機構を分子レベルで解明する.
主な方法:
- 感染した個体からの中和抗体の分離と特徴付け.
- SARS-CoV-2 感染のハムスターモデルを用いた in vivo 有効性研究.
- 抗体と抗原の相互作用の構造的基礎を決定するための冷凍電子顕微鏡.
- 様々なSARS-CoV-2単離体に対する抗体中和幅の評価.
- 抗体媒介によるエフェクター機能の評価
主要な成果:
- 2つの超強力な中和抗体,S2E12とS2M11が特定されました.
- S2E12とS2M11は,SARS-CoV-2に感染したハムスターに保護性を示した.
- 構造分析により,両方の抗体はACE2結合を阻害し,S2M11はさらに閉じた形状のスパイクタンパク質を安定させる.
- S2M11,S2E12,またはS309を含む抗体カクテルは,広範囲に循環するSARS-CoV-2単離体を中和した.
- これらの抗体はエフェクター機能を活性化します.
結論:
- 特定された抗体S2E12とS2M11は,SARS-CoV-2の予防と治療のための有望な候補である.
- 抗体カクテルは 中和を拡大し ウイルスの脱出変異体を克服する 戦略を提供します
- この発見は,SARS-CoV-2に対する抗体ベースの介入の臨床開発を支持する.
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