{
  "abstract": "Background: Antibody-dependent enhancement (ADE) is an important concern in viral infection, vaccine development, and antibody-based therapeutics. Although extensively studied in flaviviruses, the molecular mechanisms and epidemiological relevance of ADE in respiratory coronaviruses remain incompletely understood. This study aimed to investigate the epitope-specific mechanisms, cellular pathways, and population characteristics of ADE mediated by SARS-CoV-2 and MERS-CoV antibodies.\n\nMethods: SARS-CoV-2 and MERS-CoV pseudovirus ADE models were established using Fcγ receptor-expressing cells. The effects of epitope-specific antibodies, Fc–FcR interaction blockade, and inhibitors targeting Fyn, neuropilin-1 (NRP1), endosomal acidification, cathepsins, and PIKfyve were evaluated. A CD32B-based ADE model was developed for retrospective analysis of 530 human serum samples collected from 2019 to 2026. Cytokine profiles were analyzed in 175 serum samples. Correlations between antibody levels, ADE and inflammatory markers were statistically evaluated.\n\nResults: Antibodies targeting specific epitopes within coronavirus spike proteins induced ADE of both SARS-CoV-2 and MERS-CoV pseudoviruses in FcγR-expressing cells. ADE was abolished by blocking Fc–FcR interactions, confirming Fc receptor dependence. ADE induction showed a concentration- and viral load-dependent pattern, with higher viral loads requiring increased antibody concentrations for maximal enhancement. Pharmacological inhibition revealed substantial overlap between ADE and classical receptor-mediated viral entry pathways, involving Fyn signaling, NRP1, endosomal acidification, cathepsins, and PIKfyve. Analysis of clinical serum samples demonstrated a significant association between antibody levels and ADE, with ADE incidence peaking during 2023 and remaining elevated thereafter. Serum samples capable of inducing ADE exhibited altered levels of TNF-α and IL-12p70, indicating that there may be enhanced activation of Th1 and increased pro-inflammatory responses.",
  "abstract_shown": true,
  "affiliations": [
    "Pharmacological Evaluation Research Center, China State Institute of Pharmaceutical Industry",
    "Shanghai InnoStar Bio-tech Co., Ltd. (InnoStar)"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Tingting Xu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yu Jiang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chenjie Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Huaying Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhipeng Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Heng Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunliang Qiu"
    },
    {
      "affs": [
        1
      ],
      "name": "Lu Zhou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fpt6dh83trxsx.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1967945",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967945/full",
  "id": "fpt6dh83trxsx",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967945/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC581-607"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7223407337",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1967945/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fpt6dh83trxsx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1967945",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1967945/full"
    },
    {
      "first_seen": "2026-10-30T13:43:47Z",
      "native_id": "54d634d5cebe4c57948b7daa7aa48044",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fimmu.2026.1967945"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|SARS-CoV-2 and COVID-19 Research",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Integrated mechanistic and serological analyses reveal determinants of antibody-dependent enhancement in respiratory coronaviruses",
  "title_text": "Integrated mechanistic and serological analyses reveal determinants of antibody-dependent enhancement in respiratory coronaviruses",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:47Z",
  "url": "https://research.draconitic.com/paper/fpt6dh83trxsx",
  "venue": "Frontiers in Immunology",
  "versions": []
}