Benhamou, W. | 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↗

bioRxiv2024

Evolution of Virulence in Emerging Epidemics: From Theory to Experimental Evolution and Back

The experimental validation of theoretical predictions is a crucial step in demonstrating the predictive power of a model. While quantitative validations are common in infectious diseases epidemiology, experimental microbiology primarily focuses on the evaluation of a qualitative match between model predictions and experiments. In this study, we develop a method to deepen the quantitative validation process with a polymorphic viral population. We analyse the data from an experiment carried out to monitor the evolution of the temperate bacteriophage {lambda} spreading in continuous cultures of Escherichia coli. This experimental work confirmed the influence of the epidemiological dynamics on the evolution of transmission and virulence of the virus. A variant with larger propensity to lyse bacterial cells was favoured in emerging epidemics (when the density of susceptible cells was large), but counter-selected when most cells were infected. Although this approach qualitatively validated an important theoretical prediction, no attempt was made to fit the model to the data nor to further develop the model to improve the goodness of fit. Here, we show how theoretical analysis - including calculations of the selection gradients - and model fitting can be used to estimate key parameters of the phage life cycle and yield new insights on the evolutionary epidemiology of the phage {lambda}. First, we show that modelling explicitly the infected bacterial cells which will eventually be lysed improves the fit of the transient dynamics of the model to the data. Second, we carry out a theoretical analysis that yields useful approximations that capture at the onset and at the end of an epidemic the effects of epidemiological dynamics on selection and differentiation across distinct life stages of the virus. Finally, we estimate key phenotypic traits characterizing the two strains of the virus used in our experiment such as the rates of prophage reactivation or the probabilities of lysogenization. This study illustrates the synergy between experimental, theoretical and statistical approaches; and especially how interpreting the temporal variation in the selection gradient and the differentiation across distinct life stages of a novel variant is a powerful tool to elucidate the evolutionary epidemiology of emerging infectious diseases.

evolutionary biology↗