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We investigated A(H1N1)pdm09 antibody levels in sera collected from influenza cases and controls to explain the birth cohort effect of the low VE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Acute and convalescent sera were collected from adults (1986\u20132005 and 1957\u20131985 birth cohorts) during 2023\u20132024. Hemagglutination inhibiting (HI) and binding antibodies were assessed against representative A(H1N1) viruses and hemagglutinin antigens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A(H1N1)pdm09-infected cases in the 1957\u20131985 birth cohort had significantly lower HI antibodies in the acute sera against circulating A(H1N1)pdm09 viruses than 1986\u20132005 birth cohort. Over 60% of the cases in the 1957\u20131985 birth cohort had HI antibodies \u226410 to circulating A(H1N1)pdm09 viruses. Nonetheless, vaccinated cases in the same 1957\u20131985 birth cohort mounted robust antibody responses to A(H1N1)pdm09 virus infection, suggesting low vaccine immunogenicity. Antibody landscape analysis revealed that these patients born in 1957\u20131985 with the lowest VE were likely primed with USSR\/77-like A(H1N1) viruses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HI antibody levels in the acute sera were associated with protection against influenza A(H1N1)pdm09 infection. Improving the immunogenicity of the vaccines could help improve VE and overcome the birth cohort effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag294","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:42:29Z","timestamp":1780659749000},"page":"e802-e811","source":"Crossref","is-referenced-by-count":0,"title":["Birth Cohort Effects in Adults Associated With Influenza A(H1N1)pdm09 Vaccine Effectiveness"],"prefix":"10.1093","volume":"234","author":[{"given":"Feng","family":"Liu","sequence":"first","affiliation":[{"name":"Influenza Division, Centers for Disease Control and Prevention , Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F Liaini","family":"Gross","sequence":"additional","affiliation":[{"name":"Influenza Division, Centers for Disease Control and Prevention , Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhunan","family":"Li","sequence":"additional","affiliation":[{"name":"Influenza Division, Centers for Disease Control and Prevention , Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey L","family":"House","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Washington University School of Medicine , St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamair","family":"Curley","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Washington University School of Medicine , St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2514-3820","authenticated-orcid":false,"given":"Elie A","family":"Saade","sequence":"additional","affiliation":[{"name":"University Hospitals Cleveland Medical Center, School of Medicine, Case Western Reserve University , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Albar","sequence":"additional","affiliation":[{"name":"University Hospitals Cleveland Medical Center, School of Medicine, Case Western Reserve University , Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-6092","authenticated-orcid":false,"given":"Richard K","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, School of Medicine, University of Pittsburgh , Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-2690","authenticated-orcid":false,"given":"Mary Patricia","family":"Nowalk","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, School of Medicine, University of Pittsburgh , Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3952-9230","authenticated-orcid":false,"given":"Manjusha","family":"Gaglani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor Scott & White Health"},{"name":"Department of Pediatrics, Baylor College of Medicine , Temple, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5211-4144","authenticated-orcid":false,"given":"Spencer","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor Scott & White Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7368-7742","authenticated-orcid":false,"given":"Vel","family":"Murugan","sequence":"additional","affiliation":[{"name":"College of Health Solutions and Health Observatory, Arizona State University , Phoenix"},{"name":"Biodesign Center for Personalized Diagnostics, Arizona State University , Tempe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Bobbett","sequence":"additional","affiliation":[{"name":"Biodesign Center for Personalized Diagnostics, Arizona State University , Tempe"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5771-8895","authenticated-orcid":false,"given":"Emily T","family":"Martin","sequence":"additional","affiliation":[{"name":"School of Public Health, University of Michigan , Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7201-0289","authenticated-orcid":false,"given":"Ivana A","family":"Vaughn","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Henry Ford Health , Detroit, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7945-0327","authenticated-orcid":false,"given":"Karen J","family":"Wernli","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Washington Health Research Institute , Seattle, Washington"},{"name":"Department of Health System Science, Bernard J. 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