tetano
Editor, Senior Moderator
Nat Commun
. 2024 Jul 27;15(1):6338.
doi: 10.1038/s41467-024-50286-0. Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques
Marco Mandolesi[SUP] 1 [/SUP], Hrishikesh Das[SUP] 2 [/SUP], Liset de Vries[SUP] 3 [/SUP], Yiqiu Yang[SUP] 3 [/SUP], Changil Kim[SUP] 3 [/SUP], Manojj Dhinakaran[SUP] 3 [/SUP], Xaquin Castro Dopico[SUP] 3 [/SUP], Julian Fischbach[SUP] 3 [/SUP], Sungyong Kim[SUP] 3 [/SUP], Mariia V Guryleva[SUP] 3 [/SUP], Monika Àdori[SUP] 3 [/SUP], Mark Chernyshev[SUP] 3 [/SUP], Aron Stålmarck[SUP] 3 [/SUP], Leo Hanke[SUP] 3 [/SUP], Gerald M McInerney[SUP] 3 [/SUP], Daniel J Sheward[SUP] 3 [/SUP], Martin Corcoran[SUP] 3 [/SUP], B Martin Hällberg[SUP] 2 [/SUP], Ben Murrell[SUP] #[/SUP][SUP] 3 [/SUP], Gunilla B Karlsson Hedestam[SUP] #[/SUP][SUP] 4 [/SUP]
Affiliations
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.
. 2024 Jul 27;15(1):6338.
doi: 10.1038/s41467-024-50286-0. Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques
Marco Mandolesi[SUP] 1 [/SUP], Hrishikesh Das[SUP] 2 [/SUP], Liset de Vries[SUP] 3 [/SUP], Yiqiu Yang[SUP] 3 [/SUP], Changil Kim[SUP] 3 [/SUP], Manojj Dhinakaran[SUP] 3 [/SUP], Xaquin Castro Dopico[SUP] 3 [/SUP], Julian Fischbach[SUP] 3 [/SUP], Sungyong Kim[SUP] 3 [/SUP], Mariia V Guryleva[SUP] 3 [/SUP], Monika Àdori[SUP] 3 [/SUP], Mark Chernyshev[SUP] 3 [/SUP], Aron Stålmarck[SUP] 3 [/SUP], Leo Hanke[SUP] 3 [/SUP], Gerald M McInerney[SUP] 3 [/SUP], Daniel J Sheward[SUP] 3 [/SUP], Martin Corcoran[SUP] 3 [/SUP], B Martin Hällberg[SUP] 2 [/SUP], Ben Murrell[SUP] #[/SUP][SUP] 3 [/SUP], Gunilla B Karlsson Hedestam[SUP] #[/SUP][SUP] 4 [/SUP]
Affiliations
- PMID: 39068149
- PMCID: PMC11283548
- DOI: 10.1038/s41467-024-50286-0
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.