ジャーナル: Adv Sci (Weinh) / 年: 2026 タイトル: IgG-Bridging-Seeded Synergistic Aggregation of SARS-CoV-2 Spikes Underlies Potent Neutralization by a Low-Affinity Antibody. 著者: Niannian Lv / Peng Chen / Xiaobin Dai / Hu Xu / Ziheng Li / Zelin Shan / Jinqian Li / Fenglin Guo / Yuanfang Chen / Jiayi Li / Yiqian Huang / Guizhi Dong / Yifan Jiang / Liang Chen / Xuanyu ...著者: Niannian Lv / Peng Chen / Xiaobin Dai / Hu Xu / Ziheng Li / Zelin Shan / Jinqian Li / Fenglin Guo / Yuanfang Chen / Jiayi Li / Yiqian Huang / Guizhi Dong / Yifan Jiang / Liang Chen / Xuanyu Nan / Hanjun Zhao / Kang Zhang / Shilong Fan / Yuanchen Dong / Dongsheng Liu / Xinquan Wang / Deli Huang / Xiaojing Pan / Chunying Chen / Zhihua Liu / Li-Tang Yan / Qi Zhang / Linqi Zhang / Yuliang Zhao / Yuhe Renee Yang / 要旨: Mechanistic studies of viral neutralization typically prioritize high-affinity antibodies, relegating low-affinity binders to the sidelines. P5‑1C8, a Class 1 SARS-CoV-2 antibody that exemplifies ...Mechanistic studies of viral neutralization typically prioritize high-affinity antibodies, relegating low-affinity binders to the sidelines. P5‑1C8, a Class 1 SARS-CoV-2 antibody that exemplifies this underexplored "low‑affinity yet high‑potency" phenotype is reported, retaining strong neutralization of Omicron JN.1 despite markedly weakened trimer binding (K = 225 nM; IC = 0.06 nM). Structural and biophysical analyses reveal that P5-1C8 engages WT and BA.1 spikes through canonical intra-spike bivalency, but with JN.1 it induces aggregation. Using virion-like nanoparticles displaying multiple spikes, it is shown that IgG remains bound with no detectable dissociation and triggers pronounced aggregation. Coarse-grained molecular dynamics delineate the stepwise pathway in which weak IgG-spike contacts seed aggregation via transient inter-spike bridging. Together, these findings establish the first mechanistic framework demonstrating how weak-binding antibodies can nonetheless achieve potent neutralization through higher-order aggregation, thereby expanding the conceptual landscape of antibody function and opening new directions for antibody evaluation and design.