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),...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627674/full |
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| author | Fahsai Nakarin Kayla G. Sprenger |
| author_facet | Fahsai Nakarin Kayla G. Sprenger |
| author_sort | Fahsai Nakarin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e82e119049d44a528ce115bbefe0f49d |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e82e119049d44a528ce115bbefe0f49d2025-08-20T02:38:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16276741627674A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodiesFahsai Nakarin0Kayla G. Sprenger1Biomedical Engineering Graduate Program, University of Colorado Boulder, Boulder, CO, United StatesDepartment of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, United StatesBroadly 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627674/fullaffinity maturationgerminal centersimulationbroadly neutralizing antibodyB cell |
| spellingShingle | Fahsai Nakarin Kayla G. Sprenger A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies Frontiers in Immunology affinity maturation germinal center simulation broadly neutralizing antibody B cell |
| title | A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies |
| title_full | A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies |
| title_fullStr | A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies |
| title_full_unstemmed | A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies |
| title_short | A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies |
| title_sort | paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies |
| topic | affinity maturation germinal center simulation broadly neutralizing antibody B cell |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1627674/full |
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