Multivalent Antigen Display on Nanoparticles Diversifies B Cell Responses

Sebastian Ols , Klara Lenart , Rodrigo Arcoverde Cerveira , Sebastian Ols , Klara Lenart , Rodrigo Arcoverde Cerveira , Marcos C. Miranda , Natalie Brunette , Jana Kochmann , Martin Corcoran , Rebecca Skotheim , Annika Philomin , Alberto Cagigi , Brooke Fiala , Samuel Wrenn , Jessica Marcandalli , Fredrika Hellgren , Elizabeth A. Thompson , Ang Lin , Florian Gegenfurtner , Azad Kumar , Man Chen , Ganesh E. Phad , Barney S. Graham , Laurent Perez , Andrew J. Borst , Gunilla B. Karlsson Hedestam , Tracy J. Ruckwardt , Neil P. King , Karin Loré
2026 Zenodo (CERN European Organization for Nuclear Research) 0 citations

Abstract

Nanoparticles for multivalent display and delivery of vaccine antigens have emerged as a promising avenue for enhancing B cell responses to protein subunit vaccines. Here, we evaluated B cell responses in rhesus macaques immunized with prefusion stabilized Respiratory Syncytial Virus (RSV) F glycoprotein trimer compared to nanoparticles displaying 10 or 20 copies of the same antigen. We show that multivalent display skews antibody specificities and drives epitope-focusing of responding B cells. Antibody cloning and repertoire sequencing revealed that focusing was driven by expansion of clonally distinct B cells through recruitment of diverse precursors. We identified two antibody lineages that developed either ultrapotent neutralization or pneumovirus cross-neutralization from precursor B cells with low initial affinity for the RSV-F immunogen. This suggests that increased avidity by multivalent display facilitates the activation and recruitment of these cells. Diversification of the B cell response by multivalent nanoparticle immunogens has broad implications for vaccine design.

Keywords

AntigenB cellComputer scienceChemistryImmunologyAntibodyMedicine

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2026
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Sebastian Ols, Klara Lenart, Rodrigo Arcoverde Cerveira et al. (2026). Multivalent Antigen Display on Nanoparticles Diversifies B Cell Responses. Zenodo (CERN European Organization for Nuclear Research) . https://doi.org/10.5281/zenodo.7895251

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DOI
10.5281/zenodo.7895251