A Multiclass Mechanistic Model of Vaccine-Induced Humoral Response
- 1Fred Hutchinson Cancer Center
Abstract
Vaccine-induced humoral immunity emerges from complex interactions among competing B-cell populations and antibody production in response to antigen exposure, yet the mechanisms governing these interactions remain only partially understood. We developed a mechanistic mathematical model that integrates vaccine regimen features, immunogen kinetics, multiclass B-cell dynamics, and germinal center processes. The model was calibrated to data from the G001 HIV vaccine trial evaluating eOD-GT8, a germline-targeting immunogen designed to activate VRC01-class precursor B cells capable of developing into broadly neutralizing antibody-producing cells. The model reproduced key features of the observed B-cell and antibody responses, enabled estimation of class-specific activation and competition parameters, and supported investigation of the identifiability of competition parameters. Activation rates varied across B-cell classes, with memory B cells exhibiting substantially higher activation rates than naive B cells. Importantly, competition was stronger within than between classes, with the strongest competition occurring among VRC01-class B cells. These findings suggest that class-specific differences in activation and competition shape the magnitude and composition of vaccine-induced humoral response and may influence the expansion of broadly neutralizing antibody precursors. More broadly, the model provides a quantitative framework for dissecting multiclass B-cell competition and antibody responses, and for evaluating how vaccination strategies shape humoral immunity.
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BibTeX
@misc{iyaniwura2026multiclass,
title = {{A Multiclass Mechanistic Model of Vaccine-Induced Humoral Response}},
author = {S. A. Iyaniwura and B. T. Mayer and W. Hahn and S.-Y. Kim and Y. Huang and O. Hyrien},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.759230},
url = {https://www.biorxiv.org/content/10.64898/2026.10.14.759230v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Multiclass Mechanistic Model of Vaccine-Induced Humoral Response
AU - S. A. Iyaniwura
AU - B. T. Mayer
AU - W. Hahn
AU - S.-Y. Kim
AU - Y. Huang
AU - O. Hyrien
PY - 2026
DA - 2026/10/14
PB - bioRxiv
DO - 10.64898/2026.10.14.759230
UR - https://www.biorxiv.org/content/10.64898/2026.10.14.759230v1
AB - Vaccine-induced humoral immunity emerges from complex interactions among competing B-cell populations and antibody production in response to antigen exposure, yet the mechanisms governing these interactions remain only partially understood. We developed a mechanistic mathematical model that integrates vaccine regimen features, immunogen kinetics, multiclass B-cell dynamics, and germinal center processes. The model was calibrated to data from the G001 HIV vaccine trial evaluating eOD-GT8, a germline-targeting immunogen designed to activate VRC01-class precursor B cells capable of developing into broadly neutralizing antibody-producing cells. The model reproduced key features of the observed B-cell and antibody responses, enabled estimation of class-specific activation and competition parameters, and supported investigation of the identifiability of competition parameters. Activation rates varied across B-cell classes, with memory B cells exhibiting substantially higher activation rates than naive B cells. Importantly, competition was stronger within than between classes, with the strongest competition occurring among VRC01-class B cells. These findings suggest that class-specific differences in activation and competition shape the magnitude and composition of vaccine-induced humoral response and may influence the expansion of broadly neutralizing antibody precursors. More broadly, the model provides a quantitative framework for dissecting multiclass B-cell competition and antibody responses, and for evaluating how vaccination strategies shape humoral immunity.
SN - 2692-8205
ER -