Antibodies Targeting the CCHFV Nucleocapsid Protein Require TRIM21 for Protection Article Swipe
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· 2024
· Open Access
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· DOI: https://doi.org/10.21203/rs.3.rs-3915320/v1
· OA: W4391837819
<title>Abstract</title> 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 and there are currently no widely approved or highly efficacious interventions available. Recently, we reported a self-replicating, alphavirus-based RNA vaccine which 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 is protective even in mice with constitutive knock-out of Fc-gamma receptors or complement, indicating these mechanisms are not required for protection. Instead, vaccinated mice deficient in the intracellular Fc-receptor TRIM21 despite having robust CCHFV-specific immunity, were unable to control the infection. We also show that passive transfer of NP-immune sera confers significant and TRIM21-dependent protection against lethal CCHFV challenge. Together our data identifies TRIM21 as the Fc effector function of protective antibodies against the CCHFV NP and provides mechanistic insight into how vaccines against CCHFV confer protection.
