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Nucleocapsid protein-specific monoclonal antibodies protect mice against Crimean-Congo hemorrhagic fever virus

Author

Listed:
  • Aura R. Garrison

    (United States Army Medical Research Institute of Infectious Diseases)

  • Vanessa Moresco

    (University of California Riverside)

  • Xiankun Zeng

    (United States Army Medical Research Institute of Infectious Diseases)

  • Curtis R. Cline

    (United States Army Medical Research Institute of Infectious Diseases)

  • Michael D. Ward

    (United States Army Medical Research Institute of Infectious Diseases)

  • Keersten M. Ricks

    (United States Army Medical Research Institute of Infectious Diseases)

  • Scott P. Olschner

    (United States Army Medical Research Institute of Infectious Diseases)

  • Lisa H. Cazares

    (United States Army Medical Research Institute of Infectious Diseases)

  • Elif Karaaslan

    (Centers for Disease Control and Prevention)

  • Collin J. Fitzpatrick

    (United States Army Medical Research Institute of Infectious Diseases)

  • Éric Bergeron

    (Centers for Disease Control and Prevention)

  • Scott D. Pegan

    (University of California Riverside
    United States Military Academy)

  • Joseph W. Golden

    (United States Army Medical Research Institute of Infectious Diseases)

Abstract

Crimean-Congo hemorrhagic fever virus (CCHFV) is a WHO priority pathogen. Antibody-based medical countermeasures offer an important strategy to mitigate severe disease caused by CCHFV. Most efforts have focused on targeting the viral glycoproteins. However, glycoproteins are poorly conserved among viral strains. The CCHFV nucleocapsid protein (NP) is highly conserved between CCHFV strains. Here, we investigate the protective efficacy of a CCHFV monoclonal antibody targeting the NP. We find that an anti-NP monoclonal antibody (mAb-9D5) protected female mice against lethal CCHFV infection or resulted in a significant delay in mean time-to-death in mice that succumbed to disease compared to isotype control animals. Antibody protection is independent of Fc-receptor functionality and complement activity. The antibody bound NP from several CCHFV strains and exhibited robust cross-protection against the heterologous CCHFV strain Afg09-2990. Our work demonstrates that the NP is a viable target for antibody-based therapeutics, providing another direction for developing immunotherapeutics against CCHFV.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46110-4
    DOI: 10.1038/s41467-024-46110-4
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    References listed on IDEAS

    as
    1. 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.
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