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タイトル | A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 1051, Year 2024 |
掲載日 | 2024年2月5日 |
著者 | Leire de Campos-Mata / Benjamin Trinité / Andrea Modrego / Sonia Tejedor Vaquero / Edwards Pradenas / Anna Pons-Grífols / Natalia Rodrigo Melero / Diego Carlero / Silvia Marfil / César Santiago / Dàlia Raïch-Regué / María Teresa Bueno-Carrasco / Ferran Tarrés-Freixas / Ferran Abancó / Victor Urrea / Nuria Izquierdo-Useros / Eva Riveira-Muñoz / Ester Ballana / Mónica Pérez / Júlia Vergara-Alert / Joaquim Segalés / Carlo Carolis / Rocío Arranz / Julià Blanco / Giuliana Magri / |
PubMed 要旨 | Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is ...Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from a COVID-19 convalescent individual infected during the first pandemic wave. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell, with a broad neutralizing activity against former and new SARS-CoV-2 variants, including XBB.1.16 and BA.2.86 Omicron subvariants. Consistently, 17T2 demonstrates in vivo prophylactic and therapeutic activity against Omicron BA.1.1 infection in K18-hACE2 mice. Cryo-electron microscopy reconstruction shows that 17T2 binds the BA.1 spike with the RBD in "up" position and blocks the receptor binding motif, as other structurally similar antibodies do, including S2E12. Yet, unlike S2E12, 17T2 retains its neutralizing activity against all variants tested, probably due to a larger RBD contact area. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 as a potential candidate for future clinical interventions. |
リンク | Nat Commun / PubMed:38316751 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.46 - 4.41 Å |
構造データ | EMDB-16453: SARS-CoV-2 Omicron Variant Spike Trimer in complex with three 17T2 Fabs EMDB-16473, PDB-8c89: |
由来 |
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キーワード | VIRAL PROTEIN / Complex SARS-CoV-2 Spike S 17T2 |