Multivalent Antigen Display on Nanoparticles Diversifies B Cell Responses
Creators
- 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
Description
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.
Files
rsv_repo_zenodo.zip
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