RABV (Rabies virus) is a negative-stranded RNA virus of the genus Lyssavirus. RABV is a neurotropic virus that causes rabies in humans and animals. Importantly, RABV can reach the central nervous system (CNS) without triggering a strong immune response, using multiple mechanisms to evade and suppress the host immune system. Moreover, RABV causes acute, progressive encephalitis with the highest case fatality of any infectious agent. Owing to the high diversity of G protein among RABV, so the vaccine and monoclonal antibody (mAb) development has focused on RABV.
Zamerovimab (CTB011) is a mAb that binds to RABV.
Zamerovimab is a mixture of human monoclonal antibodies consisting of CTB011 and CTB012 with a 1:1 mixture of the two antibodies. Besides, Zamerovimab binds to non-overlapping epitopes on rabies virus (RABV) glycoprotein, where CTB011 binds to antigenic site III. Moreover, Zamerovimab (0.001-100 µg/mL; 4 h) induces cell death in a dose-dependent manner in virus-infected BSR cells. While Zamerovimab shows no toxicity for non-infected BSR cells. These data suggest that the cytotoxicity was specifically associated with G protein-expressing cells, which CTB011 and CTB012 target and Zamerovimab has capable of mediating complement-dependent cytotoxicity (CDC) as a mechanism of clearing RABV.
Zamerovimab shows a broad neutralization spectrum with a potency of 1700±300 IU/mg. In addition, Zamerovimab (0.03-1.0 mg/kg, right gastrocnemius injection, once, 35 days) can increase the survival of Syrian hamsters infected with RABV BD06 virus in a dose-dependent manner, with survival rates of 58%, 83%, 100% and 100% at doses of 0.03, 0.1, 0.3 and 1.0 mg/kg, respectively.
All in all, Zamerovimab is an anti-RABV mAbs, and shows the high-potency and broad-spectrum neutralization for RABV. Furthermore, Zamerovimab can be used in rabies studies.