We challenged ASC-deficient mice (ASC2/2) and wild type C57BL/6 mice intramuscularly with 5610 8 PFU rVSV as in Figures 1, 2 , and 3 and measured production of IL-1b and acute pathology after immunization. As shown in Figure 4A , the systemic and local production of IL-1b was not significantly reduced in ASC2/2 mice relative wild type control mice immunized in parallel. Consistent with that result, and with our prediction that IL-1b induces acute weight loss after rVSV infection, ASC2/2 (n = 5) mice lost slightly less weight after rVSV challenge than did wild type C57BL/6 (n = 6) mice infected in parallel, with the difference only reaching statistical significance only on the second day after challenge (P = 0.004, Mann Whitney Test, Figure 4B ). A second experiment replicated these findings almost exactly, with ASC2/2 mice (n = 6) showing slightly enhanced protection relative wild type animals (n = 10, Figure S1 ). The difference in weight loss between wild type and ASC2/2 mice was small but highly reproducible, and ASC2/2 mice were never protected to the same extent as IL-1R2/2 mice. To confirm that observation, we infected the three groups in parallel (5610 8 PFU rVSV intramuscular). As shown in Figure 4C , IL-1R2/2 mice (n = 4) lost significantly less weight than wild type (n = 5) mice (days 1-4 after challenge P,0.05 via one way ANOVA with Bonferroni multiple comparison test) and recovered their pre-immunization body weight more quickly than either wild type or ASC2/2 mice. The difference in weight loss between IL-1R2/2 and ASC2/2 mice was significant on the first and second day after challenge (P,0.05 via one way ANOVA with Bonferroni multiple comparison test). Similar to the results obtained in IL-1R2/2 mice, ASC2/2 mice made equivalent humoral responses and slightly reduced cellular responses to VSV, and were fully protected from high dose rechallenge ( Figure 4D -F). Taken together, these results demonstrated that production of IL-1b in vivo after intramuscular rVSV immunization occurred independent of inflammasome adaptor molecule ASC. Because ASC deficient mice were not protected fully from acute pathology after rVSV immunization, strategies that suppress the function of ASC would be predicted to partially but not completely abrogate acute pathology after rVSV immunization. Mice deficient in caspase-1 are partially protected from acute weight loss after immunization with rVSV vaccine vectors Similarly, when we immunized mice deficient in caspase-1 (caspase-12/2) or wild type mice with 1610 9 PFU of rVSV, caspase-1 deficient mice did not have significantly reduced levels of IL-1b relative wild type mice ( Figure 5A ) when we measured IL-1b production at the injection site and in the draining lymph node by ELISA. Consistent with those data, caspase-1 deficient mice immunized intramuscularly with 5610 8 PFU of rVSV as in Figure 4B -C (n = 5 per group), were partially but not completely protected from acute weight loss ( Figure 5B ) relative wild type mice (n = 5), with the difference in weight loss between wild type and caspase-12/2 mice being significant only on days 2 and 3 after challenge (P,0.05, Mann Whitney test). Caspase-1 deficient mice controlled viral replication as well as wild type mice ( Figure 5C , n = 6 per group), with no significant difference in viral loads in the quadriceps muscle of infected animals at 24 hours after infection. As with IL-1R2/2 mice, no virus was recovered from the blood of infected mice. Caspase-1 deficient mice made robust humoral ( Figure 5D ) and cellular ( Figure 5E ) responses to VSV, which were not significantly different than those of wild type mice.