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-Structure paper
タイトル | Stabilized coronavirus spike stem elicits a broadly protective antibody. |
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ジャーナル・号・ページ | Cell Rep, Vol. 37, Issue 5, Page 109929, Year 2021 |
掲載日 | 2021年11月2日 |
著者 | Ching-Lin Hsieh / Anne P Werner / Sarah R Leist / Laura J Stevens / Ester Falconer / Jory A Goldsmith / Chia-Wei Chou / Olubukola M Abiona / Ande West / Kathryn Westendorf / Krithika Muthuraman / Ethan J Fritch / Kenneth H Dinnon / Alexandra Schäfer / Mark R Denison / James D Chappell / Ralph S Baric / Barney S Graham / Kizzmekia S Corbett / Jason S McLellan / |
PubMed 要旨 | Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, ...Current coronavirus (CoV) vaccines primarily target immunodominant epitopes in the S1 subunit, which are poorly conserved and susceptible to escape mutations, thus threatening vaccine efficacy. Here, we use structure-guided protein engineering to remove the S1 subunit from the Middle East respiratory syndrome (MERS)-CoV spike (S) glycoprotein and develop stabilized stem (SS) antigens. Vaccination with MERS SS elicits cross-reactive β-CoV antibody responses and protects mice against lethal MERS-CoV challenge. High-throughput screening of antibody-secreting cells from MERS SS-immunized mice led to the discovery of a panel of cross-reactive monoclonal antibodies. Among them, antibody IgG22 binds with high affinity to both MERS-CoV and severe acute respiratory syndrome (SARS)-CoV-2 S proteins, and a combination of electron microscopy and crystal structures localizes the epitope to a conserved coiled-coil region in the S2 subunit. Passive transfer of IgG22 protects mice against both MERS-CoV and SARS-CoV-2 challenge. Collectively, these results provide a proof of principle for cross-reactive CoV antibodies and inform the development of pan-CoV vaccines and therapeutic antibodies. |
リンク | Cell Rep / PubMed:34710354 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.9 - 3.97 Å |
構造データ | EMDB-25072: EMDB-25073: PDB-7s3m: PDB-7s3n: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / Spike / Fusion / Antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex |