{
  "abstract": "Sequential dengue virus (DENV) infection is thought to induce long-lived protection against dengue. However, little is known about the specificity, phenotype, and repertoire of the enduring B cell response due to limitations in high-throughput methods. We used stabilized DENV envelope (E) dimers as probes for in-depth memory B cell repertoire characterization using two complementary sequencing strategies. Using Rapid Assembly, Transfection, and Production of Immunoglobulins (RATP-Ig), we isolated 227 DENV2 E dimer-specific memory B cells from an immune donor, of which 87% bound at least two serotypes, 68% bound the fusion loop (FL-sensitive), and 42% were neutralizing. Among the most neutralizing, cross-binding antibodies, the FL-sensitive antibodies had weaker but broad neutralization, including to other flaviviruses, whereas FL- agnostic antibodies mapped to E domain II and III and were potently neutralizing, but only against one or two serotypes. Competitive binding of the DENV1-4 E dimers distinguished the more potently neutralizing FL-agnostic antibodies and broad and potent anti ()- envelope dimer epitope (EDE) antibodies from the low-quality FL-sensitive antibodies. Further, analysis of the heavy chain complementarity determining region 3 (CDRH3) showed FL-sensitive and -EDE antibodies were more negatively charged, but -EDE antibodies were distinguished by longer and more aromatic CDRH3s. We then demonstrated how oligonucleotide-tagged DENV1-4 dimers and proteogenomic single-cell B cell receptor sequencing (LIBRA-seq) could identify memory B cells predicted to have potent neutralization based on DENV-binding and CDRH3 physiochemical properties. This study provides insight into the secondary DENV-specific B cell repertoire and approaches for identifying protective antibodies as part of large-screening efforts.\n\nOne Sentence SummaryApproaches to define the genetic, physicochemical, and functional properties of dengue virus envelope dimer-specific memory B cells after secondary infection.",
  "abstract_shown": true,
  "affiliations": [
    "National Institute of Allergy and Infectious Diseases, National Institutes of Health"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "name": "K. E. Lowman"
    },
    {
      "name": "R. A. Aogo"
    },
    {
      "name": "S. Smith"
    },
    {
      "name": "Y. Broderson"
    },
    {
      "name": "S. Firdous"
    },
    {
      "name": "G. Bhushan"
    },
    {
      "name": "D. J. Thiono"
    },
    {
      "name": "P. Mpingabo"
    },
    {
      "name": "A. R. Henry"
    },
    {
      "name": "T. S. Johnston"
    },
    {
      "name": "J. Roberts-Torres"
    },
    {
      "name": "L. Estrada"
    },
    {
      "name": "C. A. Schramm"
    },
    {
      "name": "F. Cheung"
    },
    {
      "name": "J. J. Polanco"
    },
    {
      "name": "R. Apps"
    },
    {
      "name": "K. Gangler"
    },
    {
      "name": "J. I. Cohen"
    },
    {
      "name": "S. Jacobson"
    },
    {
      "name": "E. Davidson"
    },
    {
      "name": "B. J. Doranz"
    },
    {
      "name": "J. Cherry"
    },
    {
      "name": "I. Douagi"
    },
    {
      "name": "B. A. Blacklaws"
    },
    {
      "name": "J. L. Heeney"
    },
    {
      "name": "A. M. de Silva"
    },
    {
      "name": "D. C. Douek"
    },
    {
      "affs": [
        0
      ],
      "name": "L. C. Katzelnick"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0gyaa9a036z23.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.15.26363039",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363039v1.full",
  "id": "0gyaa9a036z23",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363039v1",
  "language": null,
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "infectious diseases"
    ],
    [
      "openalex",
      "2739|Mosquito-borne diseases and control"
    ]
  ],
  "openalex": "W7213434937",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363039v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0gyaa9a036z23.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:45Z",
      "native_id": "10.64898/2026.09.15.26363039",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.15.26363039v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:infectious diseases",
      "subfield": "infectious-disease"
    }
  ],
  "title": "Signatures of the neutralizing dengue virus-reactive memory B cell repertoire identified by multiplexed envelope dimer probes",
  "title_text": "Signatures of the neutralizing dengue virus-reactive memory B cell repertoire identified by multiplexed envelope dimer probes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:45Z",
  "url": "https://research.draconitic.com/paper/0gyaa9a036z23",
  "venue": "medRxiv",
  "versions": []
}