Neutralization titers reveal the structure of polyclonal antibody responses
Abstract
The composition of a polyclonal antibody response is hard to measure experimentally but contains vital information about the robustness of immunity. Here, we argue that the statistics of neutralization titers alone can be used to make quantitative predictions about the composition of the response, circumventing challenges arising through sequencing and monoclonal antibody expression. We show that the response against influenza within a cohort can be either driven by a collective phenomenon where many antibodies contribute to neutralization, or dominated by just a few strong binders, leading to a broad distribution of titers across individuals described by a Gumbel distribution from extreme value theory. Comparing titers across cohorts, we find that Gumbel statistics accurately describe individuals prior to an immune challenge. We propose an equilibrium binding model that quantitatively captures titer data and illustrates the structure of the polyclonal response. Our approach extends generically to immune responses to other pathogens.
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BibTeX
@article{alston2026neutralization,
title = {{Neutralization titers reveal the structure of polyclonal antibody responses}},
author = {Henry Alston and Thierry Mora and Aleksandra Walczak},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2612096123},
eprint = {2604.11451},
archivePrefix = {arXiv},
url = {https://hal.science/hal-05820942v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Neutralization titers reveal the structure of polyclonal antibody responses
AU - Henry Alston
AU - Thierry Mora
AU - Aleksandra Walczak
PY - 2026
DA - 2026/10/07
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2612096123
UR - https://hal.science/hal-05820942v1
AB - The composition of a polyclonal antibody response is hard to measure experimentally but contains vital information about the robustness of immunity. Here, we argue that the statistics of neutralization titers alone can be used to make quantitative predictions about the composition of the response, circumventing challenges arising through sequencing and monoclonal antibody expression. We show that the response against influenza within a cohort can be either driven by a collective phenomenon where many antibodies contribute to neutralization, or dominated by just a few strong binders, leading to a broad distribution of titers across individuals described by a Gumbel distribution from extreme value theory. Comparing titers across cohorts, we find that Gumbel statistics accurately describe individuals prior to an immune challenge. We propose an equilibrium binding model that quantitatively captures titer data and illustrates the structure of the polyclonal response. Our approach extends generically to immune responses to other pathogens.
SN - 0027-8424
SN - 1091-6490
ER -