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Ultrapotent human antibodies lock E protein dimers central region of diverse DENV3 morphological variants

Author

Listed:
  • Guntur Fibriansah

    (Duke–National University of Singapore Medical School
    National University of Singapore)

  • Thiam-Seng Ng

    (Duke–National University of Singapore Medical School
    National University of Singapore)

  • Xin-Ni Lim

    (Duke–National University of Singapore Medical School
    National University of Singapore)

  • Anastasia Shebanova

    (Duke–National University of Singapore Medical School
    National University of Singapore)

  • Lee Ching Ng

    (National Environment Agency)

  • Song Ling Tan

    (Duke–National University of Singapore Medical School
    National University of Singapore)

  • Aaron W. K. Tan

    (Duke–National University of Singapore Medical School
    National University of Singapore)

  • Jian Shi

    (National University of Singapore)

  • James E. Crowe

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Shee-Mei Lok

    (Duke–National University of Singapore Medical School
    National University of Singapore)

Abstract

Dengue virus (DENV) consists of four serotypes (DENV1-4). Current vaccines induce differing levels of immune response against the four serotypes, that might prime recipients to develop severe disease in subsequent infections. Several DENV tetravalent vaccine clinical trials suggested an increased incidence in severe DENV3 cases, suggesting a need to develop DENV3 therapeutics. Human monoclonal antibodies (HMAbs) DENV-290 and DENV-115 are ultrapotent against diverse DENV3 strains with differing particle morphologies. They mainly neutralize by inhibition of virus attachment to cells. CryoEM structures of Fabs complexed with differing DENV3 morphological variants show their Fabs binding across two E protein protomers at the center of the E dimer. This new class of E protein dimer binding antibodies is named EDE-C. The cryoEM structures also show how IgGs engage the DENV particles. Results define the structural and molecular basis for the ultrapotent activity of EDE-C antibodies.

Suggested Citation

  • Guntur Fibriansah & Thiam-Seng Ng & Xin-Ni Lim & Anastasia Shebanova & Lee Ching Ng & Song Ling Tan & Aaron W. K. Tan & Jian Shi & James E. Crowe & Shee-Mei Lok, 2025. "Ultrapotent human antibodies lock E protein dimers central region of diverse DENV3 morphological variants," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-64210-7
    DOI: 10.1038/s41467-025-64210-7
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