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Here, we immunized mice with virus\u2010like particles (VLPs) from the pandemic GII.4 strain and the emergent GII.17 strain, generating monoclonal IgM and IgG antibodies via hybridoma technology. High\u2010speed atomic force microscopy visualized IgM antibodies scanning and engaging multiple protruding (P) domains on intact VLPs. Surface plasmon resonance (SPR) analyses of engineered antibodies with identical Fab sequences but different valencies revealed that, unlike monovalent IgG, multivalent IgM exhibits dramatic affinity gains\u2014up to 100\u2010fold\u2014as antigen density increases. This avidity\u2010driven enhancement arises from the dense, repetitive P\u2010domain architecture of the norovirus capsid, enabling IgM to achieve high functional affinity despite modest intrinsic Fab binding. Our findings define how antibody valency and epitope organization cooperate to boost viral recognition, offering a mechanistic framework for designing next\u2010generation vaccines and antiviral antibodies that harness multivalent engagement.<\/jats:p>","DOI":"10.1002\/pro.70522","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T04:22:06Z","timestamp":1773375726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of high affinity\n                    <scp>IgM<\/scp>\n                    and\n                    <scp>IgG<\/scp>\n                    monoclonal antibodies against norovirus variants\n                    <scp>GII<\/scp>\n                    .4 and\n                    <scp>GII<\/scp>\n                    .17"],"prefix":"10.1002","volume":"35","author":[{"given":"Jumpei","family":"Tagawa","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"},{"name":"Laboratory for Materials and Structures, Institute of Integrated research Institute of Science Tokyo  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3513-5701","authenticated-orcid":false,"given":"Saeko","family":"Yanaka","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"},{"name":"Laboratory for Materials and Structures, Institute of Integrated research Institute of Science Tokyo  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Kato","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitsu","family":"Masuda","sequence":"additional","affiliation":[{"name":"Laboratory of Creative Science for Insect Industries Kyushu University Graduate School of Bioresource and Bioenvironmental Sciences  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Man","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Creative Science for Insect Industries Kyushu University Graduate School of Bioresource and Bioenvironmental Sciences  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6911-360X","authenticated-orcid":false,"given":"Akinobu","family":"Senoo","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology Tokyo University of Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Uchihashi","sequence":"additional","affiliation":[{"name":"Graduate School of Sciences Nagoya University  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Nishida","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Kusakabe","sequence":"additional","affiliation":[{"name":"Laboratory of Insect Genome Science Kyushu University Graduate School of Bioresource and Bioenvironmental Sciences  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5568-2369","authenticated-orcid":false,"given":"Jose M. 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