Age-specific humoral immune response to SARS-CoV-2: A comparative analysis of antibody levels in children and adults after vaccination with primary series or infection
5 affiliations
- 1Epidemiology and Biostatistics Department, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona, United States of America
- 2Department of Immunobiology, University of Arizona, Tucson, Arizona, United States of America
- 3Department of Community, Environment and Policy, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, Arizona, United States of America
- 4Family and Community Medicine, College of Medicine – Tucson, University of Arizona, Tucson, Arizona, United States of America
- 5University of Arizona Genetics Core, Office for Research, Innovation and Impact, University of Arizona, Tucson, Arizona, United States of America
Abstract
Background: Age is a crucial factor in COVID-19 risk and severity, however its role in humoral immunity is unclear. This study compares associations between age and immune response following COVID-19 vaccination and SARS-CoV-2 infection. Methods: Data from the Arizona Healthcare, Emergency Response, and Other Essential Workers study (AZ-HEROES), a prospective cohort, were used to create two analytic groups: 1) a post-vaccination cohort including individuals who received two doses of the monovalent ancestral mRNA COVID-19 vaccine without prior SARS-CoV-2 infection; and 2) a post-infection cohort including unvaccinated individuals after primary infection. The analysis included data from September 2020 to April 2023. Children (<18 years) and adults (18 + years) were compared using linear regression, with immune response measured using log-transformed area under the curve (AUC) for receptor-binding domain (RBD) and spike protein subunit (S2). Finer age groups (<12, 12−17, 18−50, 50+) were also described. Adjusted models controlled for chronic conditions, medications, days since vaccination or infection, recent exposure to SARS-CoV-2 (post-vaccination only), strain type (post-infection only), and sociodemographic variables. Results: The post-vaccination analysis included 749 participants, while the post-infection analysis included 203 participants. Participants were predominantly non-Hispanic White adults, with median ages of 43 and 40 years in the post-vaccination and post-infection cohorts, respectively. Most reported no chronic conditions. In adjusted post-vaccination analysis, adults had 7% higher RBD AUC (95% CI: 1.01–1.13) and 20% higher S2 AUC (95% CI: 1.13, 1.28) than children, although these results were attenuated when restricted to individuals taking the BNT162b2 vaccine only. Post-infection, adults had 22% higher S2 AUC (95% CI: 1.05, 1.40), while RBD differences were not significant. By finer age breakdown, adolescents (12−17 years) had stronger responses than children younger than 12 post-vaccination, with 26% higher RBD AUC (95% CI: 1.13–1.40) and 29% higher S2 AUC (95% CI: 1.14–1.46). Conclusions: COVID-19 immune responses differ between children and adults, with adolescents exhibiting stronger immune response to vaccination than children younger than 12, however vaccine dosage may play a role in this observed difference. Age-related differences after infection were limited to S2 antibody responses.
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BibTeX
@article{hawkes2026agespecific,
title = {{Age-specific humoral immune response to SARS-CoV-2: A comparative analysis of antibody levels in children and adults after vaccination with primary series or infection}},
author = {Brooke A. Hawkes and James Hollister and Cynthia Porter and Zoe L. Lyski and Jefferey L. Burgess and Karen Lutrick and Shawn C. Beitel and Ryan S. Sprissler and Katherine D. Ellingson},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0356178},
url = {https://doi.org/10.1371/journal.pone.0356178},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Age-specific humoral immune response to SARS-CoV-2: A comparative analysis of antibody levels in children and adults after vaccination with primary series or infection
AU - Brooke A. Hawkes
AU - James Hollister
AU - Cynthia Porter
AU - Zoe L. Lyski
AU - Jefferey L. Burgess
AU - Karen Lutrick
AU - Shawn C. Beitel
AU - Ryan S. Sprissler
AU - Katherine D. Ellingson
PY - 2026
DA - 2026/09/02
JO - PLOS One
DO - 10.1371/journal.pone.0356178
UR - https://doi.org/10.1371/journal.pone.0356178
AB - Background: Age is a crucial factor in COVID-19 risk and severity, however its role in humoral immunity is unclear. This study compares associations between age and immune response following COVID-19 vaccination and SARS-CoV-2 infection. Methods: Data from the Arizona Healthcare, Emergency Response, and Other Essential Workers study (AZ-HEROES), a prospective cohort, were used to create two analytic groups: 1) a post-vaccination cohort including individuals who received two doses of the monovalent ancestral mRNA COVID-19 vaccine without prior SARS-CoV-2 infection; and 2) a post-infection cohort including unvaccinated individuals after primary infection. The analysis included data from September 2020 to April 2023. Children (<18 years) and adults (18 + years) were compared using linear regression, with immune response measured using log-transformed area under the curve (AUC) for receptor-binding domain (RBD) and spike protein subunit (S2). Finer age groups (<12, 12−17, 18−50, 50+) were also described. Adjusted models controlled for chronic conditions, medications, days since vaccination or infection, recent exposure to SARS-CoV-2 (post-vaccination only), strain type (post-infection only), and sociodemographic variables. Results: The post-vaccination analysis included 749 participants, while the post-infection analysis included 203 participants. Participants were predominantly non-Hispanic White adults, with median ages of 43 and 40 years in the post-vaccination and post-infection cohorts, respectively. Most reported no chronic conditions. In adjusted post-vaccination analysis, adults had 7% higher RBD AUC (95% CI: 1.01–1.13) and 20% higher S2 AUC (95% CI: 1.13, 1.28) than children, although these results were attenuated when restricted to individuals taking the BNT162b2 vaccine only. Post-infection, adults had 22% higher S2 AUC (95% CI: 1.05, 1.40), while RBD differences were not significant. By finer age breakdown, adolescents (12−17 years) had stronger responses than children younger than 12 post-vaccination, with 26% higher RBD AUC (95% CI: 1.13–1.40) and 29% higher S2 AUC (95% CI: 1.14–1.46). Conclusions: COVID-19 immune responses differ between children and adults, with adolescents exhibiting stronger immune response to vaccination than children younger than 12, however vaccine dosage may play a role in this observed difference. Age-related differences after infection were limited to S2 antibody responses.
SN - 1932-6203
ER -