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Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study
BACKGROUND: Over a life course, human adaptive immunity to antigenically mutable pathogens exhibits competitive and facilitative interactions. We hypothesize that such interactions may lead to cyclic dynamics in immune responses over a lifetime. METHODS: To investigate the cyclic behavior, we analyz...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757834/ https://www.ncbi.nlm.nih.gov/pubmed/36458815 http://dx.doi.org/10.7554/eLife.81457 |
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author | Yang, Bingyi García-Carreras, Bernardo Lessler, Justin Read, Jonathan M Zhu, Huachen Metcalf, C Jessica E Hay, James A Kwok, Kin O Shen, Ruiyun Jiang, Chao Q Guan, Yi Riley, Steven Cummings, Derek A |
author_facet | Yang, Bingyi García-Carreras, Bernardo Lessler, Justin Read, Jonathan M Zhu, Huachen Metcalf, C Jessica E Hay, James A Kwok, Kin O Shen, Ruiyun Jiang, Chao Q Guan, Yi Riley, Steven Cummings, Derek A |
author_sort | Yang, Bingyi |
collection | PubMed |
description | BACKGROUND: Over a life course, human adaptive immunity to antigenically mutable pathogens exhibits competitive and facilitative interactions. We hypothesize that such interactions may lead to cyclic dynamics in immune responses over a lifetime. METHODS: To investigate the cyclic behavior, we analyzed hemagglutination inhibition titers against 21 historical influenza A(H3N2) strains spanning 47 years from a cohort in Guangzhou, China, and applied Fourier spectrum analysis. To investigate possible biological mechanisms, we simulated individual antibody profiles encompassing known feedbacks and interactions due to generally recognized immunological mechanisms. RESULTS: We demonstrated a long-term periodicity (about 24 years) in individual antibody responses. The reported cycles were robust to analytic and sampling approaches. Simulations suggested that individual-level cross-reaction between antigenically similar strains likely explains the reported cycle. We showed that the reported cycles are predictable at both individual and birth cohort level and that cohorts show a diversity of phases of these cycles. Phase of cycle was associated with the risk of seroconversion to circulating strains, after accounting for age and pre-existing titers of the circulating strains. CONCLUSIONS: Our findings reveal the existence of long-term periodicities in individual antibody responses to A(H3N2). We hypothesize that these cycles are driven by preexisting antibody responses blunting responses to antigenically similar pathogens (by preventing infection and/or robust antibody responses upon infection), leading to reductions in antigen-specific responses over time until individual’s increasing risk leads to an infection with an antigenically distant enough virus to generate a robust immune response. These findings could help disentangle cohort effects from individual-level exposure histories, improve our understanding of observed heterogeneous antibody responses to immunizations, and inform targeted vaccine strategy. FUNDING: This study was supported by grants from the NIH R56AG048075 (DATC, JL), NIH R01AI114703 (DATC, BY), the Wellcome Trust 200861/Z/16/Z (SR), and 200187/Z/15/Z (SR). This work was also supported by research grants from Guangdong Government HZQB-KCZYZ-2021014 and 2019B121205009 (YG and HZ). DATC, JMR and SR acknowledge support from the National Institutes of Health Fogarty Institute (R01TW0008246). JMR acknowledges support from the Medical Research Council (MR/S004793/1) and the Engineering and Physical Sciences Research Council (EP/N014499/1). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
format | Online Article Text |
id | pubmed-9757834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-97578342022-12-17 Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study Yang, Bingyi García-Carreras, Bernardo Lessler, Justin Read, Jonathan M Zhu, Huachen Metcalf, C Jessica E Hay, James A Kwok, Kin O Shen, Ruiyun Jiang, Chao Q Guan, Yi Riley, Steven Cummings, Derek A eLife Epidemiology and Global Health BACKGROUND: Over a life course, human adaptive immunity to antigenically mutable pathogens exhibits competitive and facilitative interactions. We hypothesize that such interactions may lead to cyclic dynamics in immune responses over a lifetime. METHODS: To investigate the cyclic behavior, we analyzed hemagglutination inhibition titers against 21 historical influenza A(H3N2) strains spanning 47 years from a cohort in Guangzhou, China, and applied Fourier spectrum analysis. To investigate possible biological mechanisms, we simulated individual antibody profiles encompassing known feedbacks and interactions due to generally recognized immunological mechanisms. RESULTS: We demonstrated a long-term periodicity (about 24 years) in individual antibody responses. The reported cycles were robust to analytic and sampling approaches. Simulations suggested that individual-level cross-reaction between antigenically similar strains likely explains the reported cycle. We showed that the reported cycles are predictable at both individual and birth cohort level and that cohorts show a diversity of phases of these cycles. Phase of cycle was associated with the risk of seroconversion to circulating strains, after accounting for age and pre-existing titers of the circulating strains. CONCLUSIONS: Our findings reveal the existence of long-term periodicities in individual antibody responses to A(H3N2). We hypothesize that these cycles are driven by preexisting antibody responses blunting responses to antigenically similar pathogens (by preventing infection and/or robust antibody responses upon infection), leading to reductions in antigen-specific responses over time until individual’s increasing risk leads to an infection with an antigenically distant enough virus to generate a robust immune response. These findings could help disentangle cohort effects from individual-level exposure histories, improve our understanding of observed heterogeneous antibody responses to immunizations, and inform targeted vaccine strategy. FUNDING: This study was supported by grants from the NIH R56AG048075 (DATC, JL), NIH R01AI114703 (DATC, BY), the Wellcome Trust 200861/Z/16/Z (SR), and 200187/Z/15/Z (SR). This work was also supported by research grants from Guangdong Government HZQB-KCZYZ-2021014 and 2019B121205009 (YG and HZ). DATC, JMR and SR acknowledge support from the National Institutes of Health Fogarty Institute (R01TW0008246). JMR acknowledges support from the Medical Research Council (MR/S004793/1) and the Engineering and Physical Sciences Research Council (EP/N014499/1). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. eLife Sciences Publications, Ltd 2022-12-02 /pmc/articles/PMC9757834/ /pubmed/36458815 http://dx.doi.org/10.7554/eLife.81457 Text en © 2022, Yang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Epidemiology and Global Health Yang, Bingyi García-Carreras, Bernardo Lessler, Justin Read, Jonathan M Zhu, Huachen Metcalf, C Jessica E Hay, James A Kwok, Kin O Shen, Ruiyun Jiang, Chao Q Guan, Yi Riley, Steven Cummings, Derek A Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study |
title | Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study |
title_full | Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study |
title_fullStr | Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study |
title_full_unstemmed | Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study |
title_short | Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study |
title_sort | long term intrinsic cycling in human life course antibody responses to influenza a(h3n2): an observational and modeling study |
topic | Epidemiology and Global Health |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9757834/ https://www.ncbi.nlm.nih.gov/pubmed/36458815 http://dx.doi.org/10.7554/eLife.81457 |
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