Humoral immunity is required for protection from CCHFV challenge. Groups of WT or B-cell deficient μMT mice were vaccinated with 1μg of repNP + repGPC RNA or sham vaccinated in a prime-only vaccination four weeks prior to CCHFV challenge (a). On days -5 and -2 relative to CCHFV challenge, groups of repNP + repGPC vaccinated mice were treated with an isotype control or antibodies to deplete CD4 T-cells (α-CD4), CD8 T-cells (α-CD8) or both (α-CD4/ α-CD8) (a). Mice were weighed daily (b), monitored for survival (c) and body temperature monitored continuously using telemetry system (d). N = 16 for sham and 6-8 mice per other groups. Statistical comparisons performed using a two-way ANOVA with Dunnett's multiple comparisons test (b) or log-rank test with Bonferroni's correction for multiple comparisons (c). At day 5 p.i., viral loads in indicated tissues were quantified by qRT-PCR (e) and indicated statistical comparisons calculated using one-way ANOVA with Dunnett's multiple comparisons test. N = 6 per group. (b, d, e) Data shown as mean plus standard deviation. * P < 0.05, ** P < 0.01, *** P < 0.001.