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-Structure paper
| タイトル | Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 6338, Year 2024 |
| 掲載日 | 2024年7月27日 |
著者 | Marco Mandolesi / Hrishikesh Das / Liset de Vries / Yiqiu Yang / Changil Kim / Manojj Dhinakaran / Xaquin Castro Dopico / Julian Fischbach / Sungyong Kim / Mariia V Guryleva / Monika Àdori / Mark Chernyshev / Aron Stålmarck / Leo Hanke / Gerald M McInerney / Daniel J Sheward / Martin Corcoran / B Martin Hällberg / Ben Murrell / Gunilla B Karlsson Hedestam / ![]() |
| PubMed 要旨 | The continued evolution of SARS-CoV-2 underscores the need to understand qualitative aspects of the humoral immune response elicited by spike immunization. Here, we combine monoclonal antibody (mAb) ...The continued evolution of SARS-CoV-2 underscores the need to understand qualitative aspects of the humoral immune response elicited by spike immunization. Here, we combine monoclonal antibody (mAb) isolation with deep B cell receptor (BCR) repertoire sequencing of rhesus macaques immunized with prefusion-stabilized spike glycoprotein. Longitudinal tracing of spike-sorted B cell lineages in multiple immune compartments demonstrates increasing somatic hypermutation and broad dissemination of vaccine-elicited B cells in draining and non-draining lymphoid compartments, including the bone marrow, spleen and, most notably, periaortic lymph nodes. Phylogenetic analysis of spike-specific monoclonal antibody lineages identified through deep repertoire sequencing delineates extensive intra-clonal diversification that shaped neutralizing activity. Structural analysis of the spike in complex with a broadly neutralizing mAb provides a molecular basis for the observed differences in neutralization breadth between clonally related antibodies. Our findings highlight that immunization leads to extensive intra-clonal B cell evolution where members of the same lineage can both retain the original epitope specificity and evolve to recognize additional spike variants not previously encountered. |
リンク | Nat Commun / PubMed:39068149 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.6 - 2.8 Å |
| 構造データ | EMDB-17451, PDB-8p5m: EMDB-18180, PDB-8q5y: |
| 由来 |
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キーワード | VIRAL PROTEIN / Antibody / Spike / Complex / Spike. |
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