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Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus

Author

Listed:
  • Ian A. Durie

    (University of Georgia)

  • Zahra R. Tehrani

    (University of Maryland School of Medicine)

  • Elif Karaaslan

    (Centers for Disease Control and Prevention
    University of California Riverside)

  • Teresa E. Sorvillo

    (Centers for Disease Control and Prevention)

  • Jack McGuire

    (University of California Riverside)

  • Joseph W. Golden

    (United States Army Medical Research Institute of Infectious Diseases)

  • Stephen R. Welch

    (Centers for Disease Control and Prevention)

  • Markus H. Kainulainen

    (Centers for Disease Control and Prevention)

  • Jessica R. Harmon

    (Centers for Disease Control and Prevention)

  • Jarrod J. Mousa

    (University of Georgia College of Veterinary Medicine
    University of Georgia College of Veterinary Medicine)

  • David Gonzalez

    (University of California Riverside)

  • Suzanne Enos

    (University of Georgia)

  • Iftihar Koksal

    (Acibadem University Atakent Hospital)

  • Gurdal Yilmaz

    (Karadeniz Technical University School of Medicine)

  • Hanife Nur Karakoc

    (Bitlis State Hospital)

  • Sanaz Hamidi

    (Karadeniz Technical University School of Medicine)

  • Cansu Albay

    (Karadeniz Technical University School of Medicine)

  • Jessica R. Spengler

    (Centers for Disease Control and Prevention)

  • Christina F. Spiropoulou

    (Centers for Disease Control and Prevention)

  • Aura R. Garrison

    (United States Army Medical Research Institute of Infectious Diseases)

  • Mohammad M. Sajadi

    (University of Maryland School of Medicine)

  • Éric Bergeron

    (University of Georgia
    Centers for Disease Control and Prevention)

  • Scott D. Pegan

    (University of California Riverside
    United States Military Academy)

Abstract

Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.

Suggested Citation

  • Ian A. Durie & Zahra R. Tehrani & Elif Karaaslan & Teresa E. Sorvillo & Jack McGuire & Joseph W. Golden & Stephen R. Welch & Markus H. Kainulainen & Jessica R. Harmon & Jarrod J. Mousa & David Gonzale, 2022. "Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34923-0
    DOI: 10.1038/s41467-022-34923-0
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    References listed on IDEAS

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    1. Christopher O. Barnes & Claudia A. Jette & Morgan E. Abernathy & Kim-Marie A. Dam & Shannon R. Esswein & Harry B. Gristick & Andrey G. Malyutin & Naima G. Sharaf & Kathryn E. Huey-Tubman & Yu E. Lee &, 2020. "SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies," Nature, Nature, vol. 588(7839), pages 682-687, December.
    2. Bruno E. Correia & John T. Bates & Rebecca J. Loomis & Gretchen Baneyx & Chris Carrico & Joseph G. Jardine & Peter Rupert & Colin Correnti & Oleksandr Kalyuzhniy & Vinayak Vittal & Mary J. Connell & E, 2014. "Proof of principle for epitope-focused vaccine design," Nature, Nature, vol. 507(7491), pages 201-206, March.
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    Cited by:

    1. Aura R. Garrison & Vanessa Moresco & Xiankun Zeng & Curtis R. Cline & Michael D. Ward & Keersten M. Ricks & Scott P. Olschner & Lisa H. Cazares & Elif Karaaslan & Collin J. Fitzpatrick & Éric Bergeron, 2024. "Nucleocapsid protein-specific monoclonal antibodies protect mice against Crimean-Congo hemorrhagic fever virus," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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