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Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques

Author

Listed:
  • Marco Mandolesi

    (Karolinska Institutet)

  • Hrishikesh Das

    (Karolinska Institutet)

  • Liset Vries

    (Karolinska Institutet)

  • Yiqiu Yang

    (Karolinska Institutet)

  • Changil Kim

    (Karolinska Institutet)

  • Manojj Dhinakaran

    (Karolinska Institutet)

  • Xaquin Castro Dopico

    (Karolinska Institutet)

  • Julian Fischbach

    (Karolinska Institutet)

  • Sungyong Kim

    (Karolinska Institutet)

  • Mariia V. Guryleva

    (Karolinska Institutet)

  • Monika Àdori

    (Karolinska Institutet)

  • Mark Chernyshev

    (Karolinska Institutet)

  • Aron Stålmarck

    (Karolinska Institutet)

  • Leo Hanke

    (Karolinska Institutet)

  • Gerald M. McInerney

    (Karolinska Institutet)

  • Daniel J. Sheward

    (Karolinska Institutet)

  • Martin Corcoran

    (Karolinska Institutet)

  • B. Martin Hällberg

    (Karolinska Institutet)

  • Ben Murrell

    (Karolinska Institutet)

  • Gunilla B. Karlsson Hedestam

    (Karolinska Institutet)

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) 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.

Suggested Citation

  • Marco Mandolesi & Hrishikesh Das & Liset Vries & Yiqiu Yang & Changil Kim & Manojj Dhinakaran & Xaquin Castro Dopico & Julian Fischbach & Sungyong Kim & Mariia V. Guryleva & Monika Àdori & Mark Cherny, 2024. "Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50286-0
    DOI: 10.1038/s41467-024-50286-0
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