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However, designing antigens that reliably elicit bNAb responses remains challenging due to the difficulty in targeting conserved epitopes with a single antigen. We developed a method using anti\u2010idiotypic antibodies (IDs) to generate antigens that induce cross\u2010reactive antibodies against diverse influenza A and B hemagglutinins. Our approach leverages IDs that mimic the conformational epitopes targeted by bNAbs. Structural analysis reveals conformational similarity between bNAb\u2013ID and bNAb\u2013HA\u2010binding interfaces, providing mechanistic insight into molecular mimicry. These epitope\u2010mimicking IDs function as effective immunogens, inducing highly cross\u2010reactive antibodies. This study demonstrates the feasibility and structural basis of molecular mimicry\u2010based antigen design for targeting conserved conformational epitopes. Although these findings establish proof of concept, vaccine applicability requires further investigation.<\/jats:p>","DOI":"10.1002\/pro.70795","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:47:46Z","timestamp":1789480066000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti\u2010idiotypic antibodies as molecular mimics of conserved influenza hemagglutinin epitopes"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9898-8954","authenticated-orcid":false,"given":"Hiroshi","family":"Itou","sequence":"first","affiliation":[{"name":"Chiome Bioscience Inc.  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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-9542","authenticated-orcid":false,"given":"Tadaki","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Infections Disease Pathology National Institute of Infectious Diseases, Japan Institute for Health Security  Tokyo Japan"},{"name":"Department of Infectious Disease Pathobiology Graduate School of Medicine, Chiba University  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.5.2523"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1674"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ade4976"},{"key":"e_1_2_9_5_1","first-page":"1","article-title":"Immunogenicity of chimeric haemagglutinin\u2010based, universal 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