Home > Research > Publications & Outputs > Long term intrinsic cycling in human life cours...


Text available via DOI:

View graph of relations

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

Research output: Contribution to Journal/MagazineJournal articlepeer-review

  • Bingyi Yang
  • Bernardo García-Carreras
  • Justin Lessler
  • Jonathan M Read
  • Huachen Zhu
  • C Jessica E Metcalf
  • James A Hay
  • Kin O Kwok
  • Ruiyun Shen
  • Chao Q Jiang
  • Yi Guan
  • Steven Riley
  • Derek A Cummings
Article numbere81457
<mark>Journal publication date</mark>16/12/2022
Publication StatusPublished
Early online date2/12/22
<mark>Original language</mark>English


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 recog-nized 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.