Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus
Figure 5
Therapeutic efficacy of anti-CHIKV MAbs.
A. Ifnar−/− mice were passively transferred via an i.p. injection 100 µg of DENV1-E98, CHK-102, CHK-152, CHK-166, or CHK-263 or 50 µg each of CHK-102+CHK-152, CHK-166+CHK-152, CHK-263+CHK-152, or CHK-102+CHK-263 at 24 hours after CHIKV infection. B. Five week-old WT C57BL/6 mice were infected with 100 PFU of CHIKV in the footpad and either sham-treated, or treated with 100 or 50 µg of CHK-152 at 18 hours post infection. Virus induced pathology in the foot and ankle joint was assessed by histopathological analysis at day 10 post-infection. (Left) CHIKV-infected, sham-treated, (middle) CHIKV-infected, CHK-152 (100 µg) treated at +18 hours, and (right) CHIKV-infected, CHK-152 (50 µg) treated at +18 hours. Shown are representative images after hematoxylin and eosin staining from 3 mice per group at 100× magnification. Yellow and green arrows indicate regions of inflammation or normal joints, respectively. C. Ifnar−/− mice were passively transferred via an i.p. injection 200 µg of DENV1-E98 or 100 µg each of CHK-102+CHK-152, CHK-166+CHK-152, or CHK-263+CHK-152 at 48 hours after CHIKV infection. D. Ifnar−/− mice were passively transferred via an i.p. injection 500 µg of DENV1-E98 or 250 µg each of CHK-102+CHK-152 or CHK-166+CHK-152 at 60 hours after CHIKV infection. For A, C, and D the survival curves were constructed from data of at least two independent experiments. The number of animals for each antibody ranged from 8 to 10 per group, with the exception of CHK-102+CHK-263, which was performed with 7 mice only. Statistically significant differences in protection compared to DENV1-E98 are described in the text.