Multivalent Antigen Display on Nanoparticles Diversifies B Cell Responses

Tracy J. Ruckwardt; Neil P. King; Karin Loré; 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

doi:10.5281/zenodo.7895251

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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Year: 2026
Type: article
Citations: 0
Access: Closed

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APA Style

                            
                                    Tracy J. Ruckwardt, 
                                
                                    Neil P. King, 
                                
                                    Karin Loré
                                
                                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

Identifiers

DOI: 10.5281/zenodo.7895251