Antibodies targeting the Crimean-Congo Hemorrhagic Fever Virus nucleoprotein protect via TRIM21
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.
Authors
- Troy Hinkley (ORCID: https://orcid.org/0000-0003-4833-0255)
- Jesse H. Erasmus (ORCID: https://orcid.org/0000-0003-1612-2697)
- Deepashri Rao (ORCID: https://orcid.org/0000-0002-1950-962X)
- Carl Shaia (ORCID: https://orcid.org/0000-0001-8907-8821)
- Dean Clift (ORCID: https://orcid.org/0000-0001-8141-7817)
- David W. Hawman (ORCID: https://orcid.org/0000-0001-8233-8176)
- Kimberly Meade‐White (ORCID: https://orcid.org/0000-0003-0503-8174)
- Shanna Leventhal
- Thomas C. Bisom (ORCID: https://orcid.org/0000-0002-0238-1156)
- Heinz Feldmann (ORCID: https://orcid.org/0000-0001-9448-8227)
- Sonja M. Best (ORCID: https://orcid.org/0000-0003-0206-297X)
- Leo C. James (ORCID: https://orcid.org/0000-0003-2131-0334)
- Steven J. Reynolds (ORCID: https://orcid.org/0000-0002-5403-2759)
- Evan A. Mihalakakos
- Justin Murray
Institutions
- National Institutes of Health (US)
- Johns Hopkins University (US)
- MRC Laboratory of Molecular Biology (GB)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-10-25
- DOI
- https://doi.org/10.1038/s41467-024-53362-7
- Citations
- 15
- Primary Topic
- Viral Infections and Vectors
- Type
- article
- Field-Weighted Citation Impact
- 5.84
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases