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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/483| Childhood immune imprinting to influenza A shapes birth year-specific risk during seasonal H1N1 and H3N2 epidemics | |
| Rebecca Bridge Shane Brady James O Lloyd-Smith Michael Worobey Katelyn M Gostic Cecile Viboud | |
| Novel Coronavirus | |
| Acceso Abierto | |
| Atribución | |
| 10.1101/19001834 | |
| Across decades of co-circulation in humans, influenza A subtypes H1N1 and H3N2 have caused seasonal epidemics characterized by different age distributions of cases and mortality. H3N2 causes the majority of relatively severe, clinically attended cases in high-risk elderly cohorts, and the majority of overall deaths, whereas H1N1 causes fewer deaths overall, and cases shifted towards young and middle-aged adults. These contrasting age profiles may result from differences in childhood exposure to H1N1 and H3N2 or from differences in evolutionary rate between subtypes. Here we analyze a large epidemiological surveillance dataset to test whether childhood immune imprinting shapes seasonal influenza epidemiology, and if so, whether it acts primarily via immune memory of a particular influenza subtype or via broader immune memory that protects across subtypes. We also test the impact of evolutionary differences between influenza subtypes on age distributions of cases. Likelihood-based model comparison shows that narrow, within-subtype imprinting shapes seasonal influenza risk alongside age-specific risk factors. The data do not support a strong effect of evolutionary rate, or of broadly protective imprinting that acts across subtypes. Our findings emphasize that childhood exposures can imprint a lifelong immunological bias toward particular influenza subtypes, and that these cohort-specific biases shape epidemic age distributions. As a result, newer and less "senior" antibody responses acquired later in life do not provide the same strength of protection as responses imprinted in childhood. Finally, we project that the relatively low mortality burden of H1N1 may increase in the coming decades, as cohorts that lack H1N1-specific imprinting eventually reach old age. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Retrospective analysis of epidemiological surveillance data collected for another purpose. Not a clinical trial. Not a prospective study. Data did not contain identifying patient details. ### Funding Statement KG was supported by the National Institutes of Health (F31AI134017, T32-GM008185). JLS was supported by NSF grants OCE-1335657 and DEB-1557022, SERDP RC-2635, and DARPA PREEMPT D18AC00031. MW was supported by the David and Lucile Packard Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Not Applicable Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Not Applicable All data analyzed in this study, and all code necessary to perform analyses and generate figures, is freely available and archived in the Zenodo repository https://zenodo.org/badge/latestdoi/160883450. (Clearly labeled subdirectories contain the data). <https://zenodo.org/badge/latestdoi/160883450> | |
| Cold Spring Harbor Laboratory Press | |
| 2019 | |
| Preimpreso | |
| https://www.medrxiv.org/content/10.1101/19001834v2 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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| Childhood inmune imprinting.pdf | 3.42 MB | Adobe PDF | Visualizar/Abrir |