VEEV-ΔC-CHIKV protects the C57BL/6 mouse from CHIKV infection. Four groups of 4-weeks-old C57BL/6 mice (n = 5 per group) were immunized s.c. in the ventral/lateral side of the hind foot once with either 104 PFU of Δ5nsP3 or VEEV-ΔC-CHIKV; PBS was used as mock immunization. On day 30 postimmunization, mice were challenged s.c. in feet with 2.5 × 105 PFU of WT CHIKV (ECSA strain). (A) Total anti-CHIKV IgG antibodies and (B) NAb titers in mouse sera at the indicated days postimmunization. (C) Viremia and (D) footpad swelling postchallenge. All the data represent mean ± SD of group mice, and the horizontal dotted line represents the limit of detection. Student's t test or two-way ANOVA was used to determine statistical differences between groups. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001, respectively.