{
  "abstract": "Antibody-dependent enhancement (ADE) remains a major hurdle for flavivirus vaccine development. Engineering the fusion loop (FL) represents a promising solution, yet validations restricted to murine models limit human translatability due to profound species divergence. Here, we provide a primate-level demonstration that FL-engineered Zika virus (ZIKV)-M/E mRNA vaccination protects against ZIKV challenge with negligible dengue virus (DENV) ADE. The vaccine-induced B cells are overwhelmingly ZIKV specific (>97%), dominated by a convergent population using a germline ortholog of human IGHV5-10-1, a gene preferentially recruited during natural human ZIKV infection. Antibodies derived from this population are highly potent and, mechanistically, achieve multi-stage viral entry blockade. Cryo-electron microscopy analysis reveals that these antibodies target a distinct, vulnerable hotspot on ZIKV. Notably, ZIKV specificity is dictated by the epitope residues D67-M68-A69, whereas a homologous DENV N67-linked glycan imposes steric shielding to preclude cross-reactivity. Our findings demonstrate that FL engineering uncouples protective immunity from ADE for safer human flavivirus vaccines.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China",
    "University of Chinese Academy of Sciences, Beijing 100049, China",
    "College of Animal Sciences and Veterinary Medicine, Guangxi University, Nanning, Guangxi 530004, China",
    "Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China",
    "Sino-Danish College, Chinese Academy of Sciences, Beijing 100010, China",
    "National Institute of Biological Sciences (NIBS), Beijing 102206, China",
    "Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China",
    "State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430061, China",
    "Shanghai Juntuo Biomedical Technology Co Ltd., Shanghai 201210, China",
    "Department of Microbiology, Nanjing Medical University, Nanjing 211166, China",
    "Institute of Pediatrics, Shenzhen Children’s Hospital, Shenzhen 518038, China",
    "College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, China",
    "National Institute of Biological Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China",
    "Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Chenxi Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuxin Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaming Lu"
    },
    {
      "affs": [
        2
      ],
      "name": "Minrun Duan"
    },
    {
      "affs": [
        3
      ],
      "name": "Hao Yang"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Weishen He"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Yujie Cheng"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Fujian Wan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuxuan Han"
    },
    {
      "affs": [
        0
      ],
      "name": "Shengfeng Wan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Huifang Ma"
    },
    {
      "affs": [
        3
      ],
      "name": "Junbin Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Cong Tang"
    },
    {
      "affs": [
        8
      ],
      "name": "Jun Wen"
    },
    {
      "affs": [
        9
      ],
      "name": "Kun Xu"
    },
    {
      "affs": [
        10
      ],
      "name": "Sheng Liu"
    },
    {
      "affs": [
        7
      ],
      "name": "Bo Shu"
    },
    {
      "affs": [
        11
      ],
      "name": "Shuijun Zhang"
    },
    {
      "affs": [
        5,
        12,
        13
      ],
      "name": "Niu Huang"
    },
    {
      "affs": [
        3
      ],
      "name": "Shuaiyao Lu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "George F. Gao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lianpan Dai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0c0aybtm5j7pg.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103091",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710372/",
  "id": "0c0aybtm5j7pg",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103091",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2739|Mosquito-borne diseases and control"
    ]
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  "openalex": "W7220861164",
  "pdf_url": null,
  "pmcid": "PMC13710372",
  "pmid": "42843342",
  "published": "2026-10-07",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/0c0aybtm5j7pg.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:21Z",
      "native_id": "PMC13710372",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103091"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Mosquito-borne diseases and control",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Fusion-loop-engineered Zika mRNA vaccine elicits convergent B cell immunodominance to uncouple protection from ADE in macaques",
  "title_text": "Fusion-loop-engineered Zika mRNA vaccine elicits convergent B cell immunodominance to uncouple protection from ADE in macaques",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:21Z",
  "url": "https://research.draconitic.com/paper/0c0aybtm5j7pg",
  "venue": "Cell Reports Medicine",
  "versions": []
}