Cross-protection against RRVTT mediated by SCV-ZIKA/CHIK vaccinations in adult IRF3/7-/- mice. (a) Timeline of vaccination with a single dose of 106 pfu SCV-ZIKA/CHIK or SCV-Control, antibody measurements and RRVTT challenge in adult IRF3/7-/- mice; (b) CHIKV and RRVTT endpoint IgG ELISA titers after vaccination with SCV-ZIKA/CHIK or SCV-Control (limit of detection 1 in 30); (c) CHIKV and RRVTT 50% neutralization titers after vaccination with SCV-ZIKA/CHIK or SCV-Control (limit of detection 1 in 10); (d) Mean viremias post-challenge with RRVTT (n = 6 mice per group). † mice were euthanized. Statistics by t-tests; (e) Mean percentage increase in foot swelling (height x width) relative to day 0 for each foot (n = 12 feet from 6 mice per group); (f) Pictures showing examples of feet on day 0 and day 6 post-infection, illustrating swelling on day 6 in the control group; (g) Mice were scored for 1 = mild, 2 = moderate, 3 = severe for the indicated 6 disease manifestations. The mean scores for each disease manifestation for 6 mice per group are shown for SCV-ZIKA/CHIK (left) and SCV-Control vaccinated mice (right); (h) Kaplan–Meier survival curves for mice described in (g), with mice scoring 2 or more for two disease manifestations deemed to have reached ethically defined endpoints requiring euthanasia. An additional group (n = 3) were mock-vaccinated with PBS. Statistics by log rank test.