In this study, we found that IL-1R2/2 mice controlled viral loads as well as wild type control animals. Viral loads at the injection site were not significantly different between groups, and neither group had a detectable viremia after challenge. This result highlights the relative safety of the intramuscular immunization route. Equally important was that IL-1R2/2 mice challenged with VSV made robust humoral and cellular responses to VSV antigens, and were fully protected from a high dose intranasal rechallenge with VSV. Interestingly, we did observe levels of anti-VSV CD8 T cells in the IL-1R2/2 mice and in ASC2/2 mice were transiently but significantly decreased, which is consistent with the report of Iwasaki et al, who found that anti-influenza CD8 T cell responses were slightly decreased in mice with reduced levels of IL-1b production [23] . In our studies, the number of anti-VSV specific CD8 T cells was significantly lower in IL-1R2/2 and ASC2/2 mice at 14 days after infection, but was not significantly different at either 7 or 28 days after infection. This finding warrants further investigation, and follow-up studies will focus on determining whether CD8 T cells primed in the absence of IL-1 signaling are functionally different (e.g. in cytotoxic capacity, or in acquisition of central memory phenotype) from those primed in IL-1 intact animals.