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<p>Individuals exhibit considerable heterogeneity in vaccine-induced antibody responses, yet commonly used binary classifications may overlook intermediate patterns. More nuanced grouping could better capture inter-individual differences. Here, we analyzed longitudinal neutralizing antibody (NAb) trajectories in 73 adults after inactivated SARS-CoV-2 vaccination. Unsupervised analysis identified three phenotypes: Low-Delayed Responders (LR), with a modest, delayed NAb rise to day 30; Rapid-Stabilizing Responders (RS), peaking at day 7 and plateauing thereafter; and Continuous Increase Responders (CI), exhibiting sustained increases. Between days 0 and 7, these groups diverged in immune activation: LR showed limited pathway activation or cell shifts; RS exhibited early innate activation with reduced dendritic cells; CI mounted innate and adaptive responses with increased naive B cells. These differences culminated at day 7, when CI exhibited enhanced antigen presentation and Th1-related pathways, accompanied by higher IFN-γ and IL-2 T cell responses. CI also showed post-transcriptional regulation of innate signaling, including <i>HLA-F</i>/<i>H</i> splicing, 3’UTR shortening in <i>IKBKE</i> and <i>HRAS</i>, and biased <i>IGHV4-59</i>–<i>IGHJ4</i> usage. Finally, we developed a baseline gene model accurately predicting LR individuals. Our work refines responder classification and provides molecular insights into antibody heterogeneity, laying groundwork for early stratification and personalized vaccination.</p>

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Refined phenotyping of vaccine responses reveals transcriptomic determinants of neutralizing antibody heterogeneity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月30日

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  • Qingqin Wu,
  • Huajie Hu,
  • Liuyu Qin,
  • Xupu Ma,
  • Bohao Chen,
  • Xuan Li,
  • Yanli Chen,
  • Lei Xing,
  • Mei Yang,
  • Chunmei Li,
  • Zijie Scott Zhang,
  • Xuerong Pan,
  • Rui Cheng

摘要

Individuals exhibit considerable heterogeneity in vaccine-induced antibody responses, yet commonly used binary classifications may overlook intermediate patterns. More nuanced grouping could better capture inter-individual differences. Here, we analyzed longitudinal neutralizing antibody (NAb) trajectories in 73 adults after inactivated SARS-CoV-2 vaccination. Unsupervised analysis identified three phenotypes: Low-Delayed Responders (LR), with a modest, delayed NAb rise to day 30; Rapid-Stabilizing Responders (RS), peaking at day 7 and plateauing thereafter; and Continuous Increase Responders (CI), exhibiting sustained increases. Between days 0 and 7, these groups diverged in immune activation: LR showed limited pathway activation or cell shifts; RS exhibited early innate activation with reduced dendritic cells; CI mounted innate and adaptive responses with increased naive B cells. These differences culminated at day 7, when CI exhibited enhanced antigen presentation and Th1-related pathways, accompanied by higher IFN-γ and IL-2 T cell responses. CI also showed post-transcriptional regulation of innate signaling, including HLA-F/H splicing, 3’UTR shortening in IKBKE and HRAS, and biased IGHV4-59–IGHJ4 usage. Finally, we developed a baseline gene model accurately predicting LR individuals. Our work refines responder classification and provides molecular insights into antibody heterogeneity, laying groundwork for early stratification and personalized vaccination.