{
  "abstract": "Viral entry glycoproteins are often shielded from immune recognition by dense N‐linked glycans that limit antibody access to protein epitopes. While glycan‐reactive antibodies with unusual architectures have been described, how canonical Y‐shaped antibodies engage these glycan‐rich surfaces remains poorly defined. Here, we characterize two human antibodies, VRC35 and VRC36, isolated from an HIV‐1‐infected donor, that recognize diverse glycosylated viral glycoproteins. Cryo‐electron microscopy structural analyses of these antibodies in complex with viral entry glycoproteins, including HIV‐1 envelope, influenza hemagglutinin, SARS‐CoV‐2 spike, and the Lassa virus glycoprotein complex, reveal adaptive Fab stoichiometries ranging from single‐Fab binding to dimeric and higher‐order assemblies are mediated by intra‐ and inter‐IgG interactions that depend on local glycan organization. Dense glycan clustering on HIV‐1 and influenza glycoproteins supports multivalent Fab assemblies and correlates with neutralization activity, whereas sparse glycan environments on SARS‐CoV‐2 and Lassa virus favor weak or heterogeneous engagement without neutralization. Structural and mutational analyses further demonstrate that homotypic Fab–Fab interactions stabilize multivalent engagement and contribute to neutralizing activity. Together, these findings define a structural framework in which viral glycan organization constrains antibody valency and engagement, while somatic hypermutation contributes to the acquisition of homotypic Fab‐Fab interactions that facilitate multivalent recognition of viral glycan shields.",
  "abstract_shown": true,
  "affiliations": [
    "Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda Maryland USA",
    "Cellular Biology Section Laboratory of Viral Diseases National Institute of Allergy and Infectious Diseases Bethesda Maryland USA",
    "Department of Biochemistry and Molecular Biophysics and Zuckerman Mind Brain Behavior Institute Columbia University New York New York USA",
    "Aaron Diamond AIDS Research Center Columbia University Vagelos College of Physicians and Surgeons New York New York USA",
    "Drukier Institute for Children's Health Department of Pediatrics Weill Cornell Medicine New York New York USA",
    "Department of Biology Johns Hopkins University Baltimore Maryland USA",
    "Vaccine Research Center Electron Microscopy Unit Cancer Research Technology Program Frederick National Laboratory For Cancer Research Sponsored By the National Cancer Institute Frederick Maryland USA",
    "Research Technologies Branch National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda Maryland USA",
    "Laboratory of Cell Biology National Cancer Institute National Institutes of Health Bethesda Maryland USA",
    "Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda Maryland USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 72,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jiaxuan Cheng",
      "orcid": "0000-0001-9210-746X"
    },
    {
      "affs": [
        0
      ],
      "name": "Evan M. Cale"
    },
    {
      "affs": [
        0
      ],
      "name": "Amirabbas Maghsoudi",
      "orcid": "0000-0001-5874-5900"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthew S. Sutton",
      "orcid": "0009-0002-4133-3293"
    },
    {
      "affs": [
        0
      ],
      "name": "Nancy S. Longo",
      "orcid": "0009-0008-6233-9428"
    },
    {
      "affs": [
        0
      ],
      "name": "Rebecca A. Gillespie"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingshu Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Ivan Kosik"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Sue Chong",
      "orcid": "0009-0009-4946-5304"
    },
    {
      "affs": [
        4
      ],
      "name": "Atsuhiro Yasuhara"
    },
    {
      "affs": [
        0
      ],
      "name": "Tatsiana Bylund"
    },
    {
      "affs": [
        5
      ],
      "name": "Arne Schön",
      "orcid": "0000-0002-2015-2090"
    },
    {
      "affs": [
        0
      ],
      "name": "Prabhanshu Tripathi",
      "orcid": "0000-0003-1282-2848"
    },
    {
      "affs": [
        6
      ],
      "name": "Yaroslav Tsybovsky"
    },
    {
      "affs": [
        7
      ],
      "name": "Haotian Lei"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Nicholas C. Morano",
      "orcid": "0000-0002-5731-3054"
    },
    {
      "affs": [
        8
      ],
      "name": "Allison B. Lupatkin",
      "orcid": "0009-0008-8266-2193"
    },
    {
      "affs": [
        8
      ],
      "name": "Abraham J. Morton"
    },
    {
      "affs": [
        8
      ],
      "name": "Zabrina C. Lang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Jordan E. Becker"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabella R. Frascilla"
    },
    {
      "affs": [
        0
      ],
      "name": "Myungjin Lee",
      "orcid": "0000-0002-4972-3811"
    },
    {
      "affs": [
        6
      ],
      "name": "Ning Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Cuiping Liu",
      "orcid": "0000-0001-8390-1047"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Ryan S. Roark"
    },
    {
      "affs": [
        0
      ],
      "name": "Chen‐Hsiang Shen"
    },
    {
      "affs": [
        0
      ],
      "name": "I‐Ting Teng"
    },
    {
      "affs": [
        0
      ],
      "name": "David J. Van Wazer",
      "orcid": "0000-0003-4480-8282"
    },
    {
      "affs": [
        0
      ],
      "name": "Danyi Wang",
      "orcid": "0009-0008-0820-7037"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingyuan Wu",
      "orcid": "0000-0002-8548-6526"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Goran Ahlsen"
    },
    {
      "affs": [
        0
      ],
      "name": "Mike Castro"
    },
    {
      "affs": [
        0
      ],
      "name": "Haijuan Du"
    },
    {
      "affs": [
        0
      ],
      "name": "Michael J. Ernandes",
      "orcid": "0000-0001-8218-0145"
    },
    {
      "affs": [
        1
      ],
      "name": "Tiansheng Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Bob C. Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Mark K. Louder"
    },
    {
      "affs": [
        0
      ],
      "name": "Krisha McKee"
    },
    {
      "affs": [
        0
      ],
      "name": "Jonah S. Merriam",
      "orcid": "0000-0001-9203-5566"
    },
    {
      "affs": [
        0
      ],
      "name": "Sijy O'Dell"
    },
    {
      "affs": [
        0
      ],
      "name": "Li Ou",
      "orcid": "0000-0001-5653-8684"
    },
    {
      "affs": [
        0
      ],
      "name": "Sergei Pletnev"
    },
    {
      "affs": [
        1
      ],
      "name": "David Prikryl"
    },
    {
      "affs": [
        0
      ],
      "name": "Qi Qiu",
      "orcid": "0009-0003-2341-9904"
    },
    {
      "affs": [
        0
      ],
      "name": "Sarah Rubin",
      "orcid": "0009-0003-1389-7822"
    },
    {
      "affs": [
        0
      ],
      "name": "Mallika Sastry"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephen D. Schmidt"
    },
    {
      "affs": [
        0
      ],
      "name": "Asif Shajahan"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrea R. Shiakolas",
      "orcid": "0000-0001-9391-5434"
    },
    {
      "affs": [
        0
      ],
      "name": "Sanjay Srivatsan",
      "orcid": "0000-0001-7282-0487"
    },
    {
      "affs": [
        0
      ],
      "name": "Baoshan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiong Zhou"
    },
    {
      "affs": [
        9
      ],
      "name": "Mark Connors",
      "orcid": "0000-0002-2108-8705"
    },
    {
      "affs": [
        0
      ],
      "name": "Jason G. Gall",
      "orcid": "0000-0002-8411-1351"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yicheng Guo",
      "orcid": "0000-0001-5357-660X"
    },
    {
      "affs": [
        8
      ],
      "name": "Rick K. Huang"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yaoxing Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Richard A. Koup"
    },
    {
      "affs": [
        0
      ],
      "name": "Q. Paula Lei",
      "orcid": "0000-0002-3656-4014"
    },
    {
      "affs": [
        0
      ],
      "name": "John R. Mascola"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bc97b6ysv8azt.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.77172",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13474179/",
  "id": "bc97b6ysv8azt",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.77172",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2741|Monoclonal and Polyclonal Antibodies Research"
    ]
  ],
  "openalex": "W7203458002",
  "pdf_url": null,
  "pmcid": "PMC13474179",
  "pmid": "42598737",
  "published": "2026-08-14",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/bc97b6ysv8azt.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:23:13Z",
      "native_id": "PMC13474179",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.77172"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "imaging"
    }
  ],
  "title": "Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields",
  "title_text": "Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:32Z",
  "url": "https://research.draconitic.com/paper/bc97b6ysv8azt",
  "venue": "Advanced Science",
  "versions": []
}