High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

Michelow, Ian C.; Lear, Calli; Scully, Corinne; Prugar, Laura I.; Longley, Clifford B.; Yantosca, L. Michael; Ji, Xin; Karpel, Marshall; Brudner, Matthew; Takahashi, Kazue; Spear, Gregory T.; Ezekowitz, R. Alan B.; Schmidt, Emmett V.; Olinger, Gene G.

Ebola and Marburg viruses of the filovirus family are among the most virulent causes of the human viral hemorrhagic fevers and cause devastating epidemics of fulminant and rapidly fatal disease. They constitute important biological threat agents because of their high mortality rates, capacity for large-scale dissemination, and potential for causing social disruption. Currently, there are no US Food and Drug Administrationapproved therapeutic agents available to prevent or treat these lethal viral infections. Filovirus surface glycoproteins (GPs) are heavily glycosylated and contain high-mannose. As a result, MBL binds to Ebola and Marburg viruses and mediates complement-dependent virus neutralization [2] . Importantly, their surface glycoprotein structures are characteristic of a broad group of viruses in which N-linked glycosylation contributes to viral virulence [7] . Reasoning that MBL treatment is likely to be safe at supraphysiological levels, we evaluated an in vivo Ebola virus model to explore the possibility of using MBL as an immunotherapeutic agent. Our results showed that supraphysiological doses of MBL rescued $40% of mice from lethal challenges when administered pre-or post-Ebola virus exposure.