Figure 5
Evaluation of in vivo toxicity and anti-CHIKV efficacy of CPMO1v in neonate murine model.
(a) BALB/c mice (6-day old, n = 6 per group) were intraperitoneally (i.p) injected with sterile PBS, anti-CHIKV vivo-PMO (CPMO1v) or scrambled vivo-PMO (sCPMO1v) at 5 μg/g, 10 μg/g or 15 μg/g consecutively for seven days at every 24 h interval. Mice were sacrificed at 6 h after the last treatment and whole blood was harvested for quantification of LDH activity level. (b) In survival study, two dose of sterile PBS, CPMO1v or sCPMO1v at 5 μg/g or 15 μg/g were given via i.p to neonate mice (n = 6 per group) at 24 h interval, followed by CHIKV infection at 4 × 105 PFU. Treatment was given at two more equivalent doses at 18 h p.i. and 42 h p.i. and mice were monitored daily for sign or symptom of CHIKV morbidity as well as (c) their daily weight gain over two weeks. At the end of two weeks p.i., the number of surviving mice was recorded and presented on Kaplan-Meier chart. A dose-dependent protection is observed in CPMO1v-treated mice relative to the PBS- and sCPMO1v- control groups. (d–h) Mice (n = 5 per group) were subjected to the same treatment regimen above. At 48 h p.i., (d) whole blood, (e) spleen, (f) liver, (g) brain and (h) hind limbs were harvested and homogenized for viral plaque assays. Significant reduction in viremia and CHIKV load were observed. Statistical analysis is done using one-way ANOVA across all groups followed by unpaired one-tailed t-test. (*p < 0.05, **p < 0.005, ***p < 0.0005; Graphpad prism 6).
