{
  "abstract": "Despite advances in HIV-1 envelope glycoprotein (Env)-based vaccine design, eliciting broadly neutralizing antibodies (bNAbs) remains a central challenge. Here, we identify core (1,3)-fucose as a key modulator of neutralizing antibody (NAb) induction and breadth. Uncleaved prefusion-optimized (UFO) trimers and self-assembling protein nanoparticles (SApNPs) produced in High Five (Hi5) insect cells incorporate core (1,3)-fucose into the Env glycan shield. Crystal structures of Hi5-produced BG505 UFO trimers in complex with bNAbs confirm native-like Env architecture and epitope presentation. In wild-type mice, these trimers and SApNPs elicit robust autologous and heterologous NAb responses. We then engineer Chinese hamster ovary (CHO) cells to co-express three insect- and plant-derived core (1,3)-fucosyltransferases. The resulting immunogens carry fucosylated mammalian glycans and elicit cross-clade NAb responses in mice, supporting an important role for core (1,3)-fucose in broadened neutralization. Env-specific IgE responses suggest engagement of associated immune pathways during vaccination. In ATX-Gx humanized mice, core (1,3)-fucosylated, glycan-trimmed Env elicits detectable cross-clade neutralization by week 11. Single-cell analysis identifies distinct human antibody lineages with cross-clade activity and noncanonical Env recognition. Repertoire and functional analyses uncover putatively related lineage members across two animals within the same group. Together, these findings support xenoglycosylation as a promising, germline-agnostic strategy for HIV-1 vaccine design.",
  "abstract_shown": true,
  "affiliations": [
    "The Scripps Research Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "L. He"
    },
    {
      "name": "X. Lin"
    },
    {
      "name": "Y.-N. Zhang"
    },
    {
      "name": "M. L. Newby"
    },
    {
      "name": "C. DesRoberts"
    },
    {
      "name": "J. D. Allen"
    },
    {
      "name": "R. D. Stanfield"
    },
    {
      "name": "M. Crispin"
    },
    {
      "name": "I. A. Wilson"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Zhu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/08vkt1fne7e2v.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757767",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757767v1.full",
  "id": "08vkt1fne7e2v",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757767v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2406|HIV Research and Treatment"
    ]
  ],
  "openalex": "W7222152799",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757767v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/08vkt1fne7e2v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:59Z",
      "native_id": "10.64898/2026.10.08.757767",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757767v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Xenoglycosylation of the HIV-1 Glycan Shield Promotes Cross-Clade Neutralization and Diverse Human Antibody Lineages",
  "title_text": "Xenoglycosylation of the HIV-1 Glycan Shield Promotes Cross-Clade Neutralization and Diverse Human Antibody Lineages",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:59Z",
  "url": "https://research.draconitic.com/paper/08vkt1fne7e2v",
  "venue": "bioRxiv",
  "versions": []
}