Howerton, E. | bioRxiv Science

bioRxiv2026

Vaccine imprinting drives increased SARS-CoV-2 variant infection in children

Virus exposure history, particularly first exposure, is believed to shape vaccine efficacy and infection susceptibility; however, evidence for mechanistic links between immune responses in individuals and epidemiological outcome in populations is scarce. Recent co-circulation of SARS-CoV-2 variants XFG and BA.3.2 has revealed a striking enrichment in BA.3.2 cases among children. By combining epidemiological modeling, serology and monoclonal antibody analysis in children and adults, we show the dependence of effective variant-specific antibodies on vaccination history which may explain birth-year influence on differential susceptibility to these co-circulating variants. Ancestral cross-reactive site I antibodies frequently neutralize BA.3.2, but not XFG. By contrast, Omicron type-specific site I/III and III antibodies frequently neutralize XFG but not BA.3.2, revealing a tradeoff in the ability to neutralize these two co-circulating strains. These findings mechanistically link immune history, variant neutralization, antibody repertoire and variant infection risk, and suggest that vaccination regimens in children should prioritize neutralization breadth.

immunology↗

bioRxiv2025

Susceptible host dynamics explain pathogen resilience to perturbations

Interventions to slow the spread of SARS-CoV-2 significantly disrupted the transmission of other pathogens. As interventions lifted, whether and when human pathogens would eventually return to their pre-pandemic dynamics remains to be answered. Here, we present a framework for estimating pathogen resilience based on how fast epidemic patterns return to their pre-pandemic dynamics. By analyzing time series data from Hong Kong, Canada, Korea, and the US, we quantify the resilience of common respiratory pathogens and further predict when each pathogen will eventually return to its pre-pandemic dynamics. Our predictions are able to distinguish which pathogens should have returned already, and deviations from these predictions reveal long-term impacts of pandemic perturbations. We find a faster rate of susceptible replenishment underlies pathogen resilience and sensitivity to both large and small perturbations. Overall, our analysis highlights the persistent nature of common respiratory pathogens compared to vaccine-preventable infections, such as measles. Significance StatementCOVID-19 interventions slowed the transmission of many respiratory pathogens in different ways, raising questions about the mechanisms driving the variation in responses to interventions. To address this gap, we characterized the sensitivity of pathogen transmission to perturbations by quantifying how fast each pathogen returned to its pre-pandemic circulation patterns. We analyzed data from Hong Kong, Canada, Korea, and the US, and showed that common respiratory pathogens are far less sensitive to perturbations than measles, a vaccine-preventable infection. Finally, we showed that the speed of replenishment of the susceptible population--for example, through waning immunity--largely determines this sensitivity, suggesting that the persistence of common respiratory pathogens is likely driven by rapid susceptible replenishment.

ecology↗