+Search query
-Structure paper
Title | Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques. |
---|---|
Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 6338, Year 2024 |
Publish date | Jul 27, 2024 |
Authors | 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 Abstract | 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. |
External links | Nat Commun / PubMed:39068149 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.6 Å |
Structure data | EMDB-18180, PDB-8q5y: |
Source |
|
Keywords | VIRAL PROTEIN / Antibody / Spike. |