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.

We monitored the effect of treatment started 12 hours after infection on a variety of laboratory indices. Mean white blood cell counts were 9100 cells/mL in MBL-treated mice (n 5 5) compared with 4525 cells/mL on day 7 after infection in the surviving sham-treated mice (n 5 4). Average lymphocyte counts were also higher in MBL-treated mice compared with controls (5500 cells/mL vs 2800 cells/mL, respectively). A similar trend was seen for platelet counts, which averaged 726,000 cells/ mL in the treatment group and 239,000 cells/mL in the controls. These differences were statistically significant for platelet counts on day 5 (672,000 cells/mL vs 322,000 cells/mL, P 5 .014; Figure 1C ). In a separate experiment, spleens were harvested on day 5 after infection (4 sham-treated and 4 MBL-treated mice). Constituent cell populations were assayed by flow cytometry. Numbers of splenic CD3 2 CD19 1 cells (B lymphocytes) and CD11b 1 granulocytes were higher in MBL-treated mice (89.2% vs 85.1%, P 5 .019; 17.6% vs 12.8%, P 5 .04, respectively). The RNA viral loads as determined by RT-PCR in blood, liver, and spleen 5 days after infection were similar in sham-and rhMBL-treated mice (P . .05). Virus titers in blood were generally lower on days 1 and 3 in rhMBL-treated mice as determined by plaque assays (P . .05; Figure 1D ). Of 23 cytokines and chemokines tested in serum, liver, and spleen on day 5 after inoculation, lower values (fluorescence intensity units) for interleukin (IL)-1b (170 vs 253, P 5 .07), IL-5 (89 vs 112, P 5 .03), IL-10 (379 vs 518, P 5 .004), IL-13 (264 vs 384, P 5 .008), and IL-17 (120 vs 174, P 5 .028) were found in liver homogenates from rhMBL-treated mice ( Figure 1E ). We tested protective immunity in 5 seropositive mice that survived initial infection by rechallenging them with native Ebola virus 28 days after initial infection. It is noteworthy that all MBL-treated survivors also survived the second viral challenge. Similar or higher immunoglobulin G, A, and M antibody titers were seen 28 days after the second challenge with the virus ( Figure 1F ).