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P5\u20111C8, a Class\u00a01 SARS\u2010CoV\u20102 antibody that exemplifies this underexplored \u201clow\u2011affinity yet high\u2011potency\u201d phenotype is reported, retaining strong neutralization of Omicron JN.1 despite markedly weakened trimer binding (K\n                    <jats:sub>D<\/jats:sub>\n                    = 225 nM; IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.06 nM). Structural and biophysical analyses reveal that P5\u20101C8 engages WT and BA.1 spikes through canonical intra\u2010spike bivalency, but with JN.1 it induces aggregation. Using virion\u2010like nanoparticles displaying multiple spikes, it is shown that IgG remains bound with no detectable dissociation and triggers pronounced aggregation. Coarse\u2010grained molecular dynamics delineate the stepwise pathway in which weak IgG\u2010spike contacts seed aggregation via transient inter\u2010spike bridging. Together, these findings establish the first mechanistic framework demonstrating how weak\u2010binding antibodies can nonetheless achieve potent neutralization through higher\u2010order aggregation, thereby expanding the conceptual landscape of antibody function and opening new directions for antibody evaluation and design.\n                  <\/jats:p>","DOI":"10.1002\/advs.202517192","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T05:26:59Z","timestamp":1765171619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["IgG\u2010Bridging\u2013Seeded Synergistic Aggregation of SARS\u2010CoV\u20102 Spikes Underlies Potent Neutralization by a Low\u2010Affinity Antibody"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7405-4069","authenticated-orcid":false,"given":"Niannian","family":"Lv","sequence":"first","affiliation":[{"name":"National Cancer 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