Vaccine imprinting drives increased SARS-CoV-2 variant infection in children
Johnston, T. S.; Subramanian, R.; Benhamou, W.; Howerton, E.; Schlesinger, R.; Schmidt, S. D.; Kazmierski, R.; Castro, M.; Lin, B. C.; Henry, A. R.; Smith, S. C.; Roberts-Torres, J.; Laboune, F.; Teng, I.-T.; Wang, S.; Isiofia, D.; Dong, L.; Painter, M. M.; Spaulding, A. B.; Schramm, C. A.; Kimberlin, D. W.; Dominguez, S. R.; Nguyen-Tran, H.; Permaul, P.; Wherry, E. J.; Vogt, M. R.; Messacar, K.; Zhou, T.; Serebryannyy, L. A.; Grenfell, B. T.; Douek, D. C.
Show abstract
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.
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