A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies
Broadly neutralizing antibodies (bnAbs) offer a promising route to protect against rapidly evolving pathogens such as HIV, influenza, and SARS-CoV-2, yet eliciting them through vaccination remains a significant challenge. A key to this problem lies in understanding antibody affinity maturation (AM),...
Bewaard in:
| Hoofdauteurs: | , |
|---|---|
| Formaat: | Artikel |
| Taal: | Engels |
| Gepubliceerd in: |
Frontiers Media S.A.
2025-07-01
|
| Reeks: | Frontiers in Immunology |
| Onderwerpen: | |
| Online toegang: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627674/full |
| Tags: |
Voeg label toe
Geen labels, Wees de eerste die dit record labelt!
|
| Samenvatting: | Broadly neutralizing antibodies (bnAbs) offer a promising route to protect against rapidly evolving pathogens such as HIV, influenza, and SARS-CoV-2, yet eliciting them through vaccination remains a significant challenge. A key to this problem lies in understanding antibody affinity maturation (AM), the evolutionary process within germinal centers (GCs) that shapes the B cell and thus antibody response. Traditionally, AM has been viewed as favoring the selection of B cells with the highest-affinity B cell receptors (BCRs) through competitive interplays. However, emerging evidence suggests that GCs are more permissive, allowing B cells with a broad range of affinities to persist, thereby promoting clonal diversity and enabling the rare emergence of bnAbs. This review reassesses affinity-based selection models and proposes a new paradigm that integrates multifactorial processes, including stochastic B cell decisions within GC dynamics, antigen extraction efficiency influenced by probabilistic bond rupture, and avidity-driven BCR binding alterations and representations on multivalent antigens. We highlight how advanced AM simulations that move beyond affinity as the sole determinant provide a more realistic and predictive representation of AM, marking a major step forward in developing strategies to promote effective immune responses against highly mutable, complex antigens. |
|---|---|
| ISSN: | 1664-3224 |