{"doi":"10.1101/2022.06.27.22276898","title":"Long-term intrinsic cycling in human life-course antibody responses to influenza A(H3N2)","abstract":"ABSTRACT 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. Here, we demonstrated a long-term periodicity (about 24 years) in individual antibody responses, by analyzing hemagglutination inhibition titers against 21 historical influenza A(H3N2) strains spanning 47 years from a cohort in Guangzhou, China. 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 response to circulating strains, after accounting for age and pre-existing titers of the circulating strains. 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.","journal":"medRxiv","year":2022,"id":309529,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.943,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":60895,"name":"Bernardo García-Carreras","orcid":"0000-0002-0714-300X","position":1,"is_corresponding":false},{"id":78334,"name":"Justin Lessler","orcid":"0000-0002-9741-8109","position":2,"is_corresponding":false},{"id":339531,"name":"Jonathan M. Read","orcid":"0000-0002-9697-0962","position":3,"is_corresponding":false},{"id":104800,"name":"Huachen Zhu","orcid":"0000-0003-2711-0501","position":4,"is_corresponding":false},{"id":228273,"name":"C. Jessica E. Metcalf","orcid":"0000-0003-3166-7521","position":5,"is_corresponding":false},{"id":87617,"name":"James A. Hay","orcid":"0000-0002-1998-1844","position":6,"is_corresponding":false},{"id":339532,"name":"Kin On Kwok","orcid":"0000-0002-2804-5433","position":7,"is_corresponding":false},{"id":340841,"name":"Ruiyin Shen","orcid":null,"position":8,"is_corresponding":false},{"id":339530,"name":"Chao Qiang Jiang","orcid":"0000-0001-6589-1068","position":9,"is_corresponding":false},{"id":104820,"name":"Yi Guan","orcid":"0000-0001-6057-9243","position":10,"is_corresponding":false},{"id":339533,"name":"Steven Riley","orcid":"0000-0001-7904-4804","position":11,"is_corresponding":false},{"id":107139,"name":"Derek A. T. Cummings","orcid":"0000-0002-9437-1907","position":12,"is_corresponding":false},{"id":107128,"name":"Bingyi Yang","orcid":"0000-0002-0811-8332","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-19T00:33:11.579763Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}