Recombinant Bombali ebolavirus in cynomolgus macaques as a survival model of Ebola virus disease

Ebolaviruses are known to cause severe hemorrhagic fever in humans. A new ebolavirus species, Bombali orthoebolavirus (BOMV), was recently detected in bats from Sierra Leone, Kenya, Guinea, Mozambique, and Tanzania. No infectious BOMV has been isolated from field samples, but an infectious recombinant BOMV clone (rBOMV) was recently established. To estimate disease potential in humans, we challenged cynomolgus macaques with rBOMV. Macaques exhibit hallmark features of Ebola virus disease, including vascular leak, lymphopenia, neutrophilia, and elevated inflammation markers. Consistent with these hallmarks, we detected rBOMV in multiple target tissues at peak viremia, including the liver, lymph nodes, and adrenal gland. All animals survive challenge and develop robust adaptive immune responses, including strong BOMV-specific IgG and neutralizing antibody titers. These data suggest that BOMV may have an attenuated disease phenotype compared to more pathogenic ebolaviruses such as Ebola, Bundibugyo, Sudan, or Taï Forest and may serve as an important model of resolving Ebola Virus Disease.