التفاصيل البيبلوغرافية
| العنوان: |
Multivalent antigen display on nanoparticle immunogens increases B cell clonotype diversity and neutralization breadth to pneumoviruses. |
| المؤلفون: |
Ols, Sebastian1,2 (AUTHOR), Lenart, Klara1,2 (AUTHOR), Arcoverde Cerveira, Rodrigo1,2 (AUTHOR), Miranda, Marcos C.1,2 (AUTHOR), Brunette, Natalie3,4 (AUTHOR), Kochmann, Jana1,2 (AUTHOR), Corcoran, Martin5 (AUTHOR), Skotheim, Rebecca3,4 (AUTHOR), Philomin, Annika3,4 (AUTHOR), Cagigi, Alberto1,2 (AUTHOR), Fiala, Brooke3,4 (AUTHOR), Wrenn, Samuel3,4 (AUTHOR), Marcandalli, Jessica6 (AUTHOR), Hellgren, Fredrika1,2 (AUTHOR), Thompson, Elizabeth A.1,2 (AUTHOR), Lin, Ang1,2 (AUTHOR), Gegenfurtner, Florian1,2 (AUTHOR), Kumar, Azad7 (AUTHOR), Chen, Man7 (AUTHOR), Phad, Ganesh E.5,6 (AUTHOR) |
| المصدر: |
Immunity (10747613). Oct2023, Vol. 56 Issue 10, p2425-2425. 1p. |
| مصطلحات موضوعية: |
*B cells, *NANOPARTICLES, *NANOPARTICLE size, *ANTIGENS, *ANTIBODY specificity |
| مستخلص: |
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 with 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 the 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. [Display omitted] • Increased immunogen size slows kinetics of antigen accumulation in lymph nodes • High antigen valency restricts access to base-proximal epitopes on displayed antigens • Avidity effects from higher valency drive recruitment of more diverse B cell clonotypes • Antibodies with high potency or breadth can affinity mature from low-affinity precursors A mechanistic understanding of immune responses elicited by multivalent nanoparticle immunogens is lacking in higher mammals. Ols et al. show in non-human primates that humoral responses are modulated by interrelated aspects of nanoparticles: their size and valency. Nanoparticle size slowed lymphatic transport, and valency-dependent avidity improved recruitment of low-affinity B cells, increasing B cell clonotype diversity and neutralization breadth. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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