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.

Biological responses of the infected mice to rhMBL treatment further indicated that our strategy targeted the main pathogenic effects of Ebola viruses. MBL-treated mice had higher B lymphocyte and CD11b 1 granulocyte counts and demonstrated down-regulation of intrahepatic proinflammatory (IL-1b and IL-17) and Th2 cytokines (IL-5, IL-10, and IL-13) early in the course of infection ( Figure 1E ), suggesting that rhMBL may mitigate the detrimental effects of the characteristic cytokine storm. MBL-treated mice tended to have greater inhibition of viral replication on days 1 and 3 after infection (P . .05; Figure 1D ). Most important, rhMBL treatment bridged surviving mice to development of an effective adaptive immune response ( Figure 1F) . Future experiments will be needed to scale high-dose rhMBL therapy for use in larger animal models and to test rhMBL in combination with other promising experimental therapies such as small molecule inhibitors, coagulation modulators, antisense technologies, therapeutic antibodies and NOTE. RhMBL was administered by a single intraperitoneal injection. Data are arithmetic mean (6SEM). Statistical differences were analyzed with the Student t-test (2-tailed). A value of P , .05 was considered to indicate a statistically significant difference. rhMBL, recombinant human mannose-binding lectin.