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PLoS One
. 2026 Sep 2;21(9):e0356178.
doi: 10.1371/journal.pone.0356178. eCollection 2026.
Brooke A Hawkes 1 , James Hollister 1 , Cynthia Porter 1 , Zoe L Lyski 2 , Jefferey L Burgess 3 , Karen Lutrick 4 , Shawn C Beitel 3 , Ryan S Sprissler 5 , Katherine D Ellingson 1
Affiliations
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.
. 2026 Sep 2;21(9):e0356178.
doi: 10.1371/journal.pone.0356178. eCollection 2026.
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
Brooke A Hawkes 1 , James Hollister 1 , Cynthia Porter 1 , Zoe L Lyski 2 , Jefferey L Burgess 3 , Karen Lutrick 4 , Shawn C Beitel 3 , Ryan S Sprissler 5 , Katherine D Ellingson 1
Affiliations
- PMID: 42685055
- DOI: 10.1371/journal.pone.0356178
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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