Crimean-Congo Hemorrhagic Fever Virus (CCHFV) is a negative-sense RNA virus with no widely approved or highly efficacious interventions. A self-replicating alphavirus-based RNA vaccine expressing the CCHFV nucleoprotein (NP) is protective. This study shows this vaccine generates neutralizing anti-N antibodies and that protection doesn't require Fc-gamma receptors or complement. Instead, protection is mediated by TRIM21, and passive transfer of NP-immune antibodies provides TRIM21-dependent protection against lethal CCHFV challenge. This identifies TRIM21-mediated mechanisms as the effective function of protective antibodies against CCHFV NP.

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