Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modelling study

Yang, Bingyi and García-Carreras, Bernardo and Lessler, Justin and Read, Jonathan M and Zhu, Huachen and Metcalf, C Jessica E and Hay, James A and Kwok, Kin O and Shen, Ruiyun and Jiang, Chao Q and Guan, Yi and Riley, Steven and Cummings, Derek A (2022) Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modelling study. eLife, 11. ISSN 2050-084X

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Abstract

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 explain 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 pre-existing 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.

Item Type:
Journal Article
Journal or Publication Title:
eLife
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800
Subjects:
ID Code:
181463
Deposited By:
Deposited On:
16 Dec 2022 13:50
Refereed?:
Yes
Published?:
Published
Last Modified:
16 Dec 2022 13:50