Nature Communications (Oct 2024)

Antibodies targeting the Crimean-Congo Hemorrhagic Fever Virus nucleoprotein protect via TRIM21

  • Shanna S. Leventhal,
  • Thomas Bisom,
  • Dean Clift,
  • Deepashri Rao,
  • Kimberly Meade-White,
  • Carl Shaia,
  • Justin Murray,
  • Evan A. Mihalakakos,
  • Troy Hinkley,
  • Steven J. Reynolds,
  • Sonja M. Best,
  • Jesse H. Erasmus,
  • Leo C. James,
  • Heinz Feldmann,
  • David W. Hawman

DOI
https://doi.org/10.1038/s41467-024-53362-7
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 14

Abstract

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Abstract Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a negative-sense RNA virus spread by Hyalomma genus ticks across Europe, Asia, and Africa. CCHF disease begins as a non-specific febrile illness which may progress into a severe hemorrhagic disease with no widely approved or highly efficacious interventions currently available. Recently, we reported a self-replicating, alphavirus-based RNA vaccine that expresses the CCHFV nucleoprotein and is protective against lethal CCHFV disease in mice. This vaccine induces high titers of non-neutralizing anti-NP antibodies and we show here that protection does not require Fc-gamma receptors or complement. Instead, vaccinated mice deficient in the intracellular Fc-receptor TRIM21 were unable to control the infection despite mounting robust CCHFV-specific immunity. We also show that passive transfer of NP-immune sera confers significant TRIM21-dependent protection against lethal CCHFV challenge. Together our data identifies TRIM21-mediated mechanisms as the Fc effector function of protective antibodies against the CCHFV NP and provides mechanistic insight into how vaccines against the CCHFV NP confer protection.