Live-attenuated Rift Valley fever virus vaccination leads to durable, protective immunity independent of sex in C57BL/6 mice

Abstract Background Rift Valley fever virus (RVFV) is a zoonotic arbovirus endemic to Africa and the Arabian Peninsula that can cause disease in humans and livestock. There are currently no licensed vaccines for human use, but several candidates are at the clinical trial stage including DDVaxTM, a preparation of live-attenuated RVFV lacking the nonstructural proteins NSs and NSm (ΔNSsΔNSm). Multiple pre-clinical studies have shown that ΔNSsΔNSm is safe and immunogenic. Methods The longitudinal study described in this manuscript examined the additional features of duration, sex and dose in immunogenicity and protection provided by ΔNSsΔNSm. Female and male 8-week-old C57BL/6 mice were vaccinated with either a low- or high-dose of ΔNSsΔNSm and humoral (via neutralization assay and ELISA) and cellular immunity (ELISPOT and flow cytometry) were assessed over a period of 6 months. A subset of animals were challenged with a lethal dose of wild type (WT) RVFV 6 months post-vaccination. Results All vaccinated animals were protected against lethal Rift Valley fever (RVF) disease 6 months post-vaccination independent of dose or sex. Humoral immunity in the form of RVFV-specific neutralizing and binding antibodies decreased over time but remained detectable at the end of the study. RVFV-specific CD4+ T cells also decreased by 6 months post-vaccination. In contrast, virus-specific polyfunctional CD8+ T cells persisted at comparable levels throughout the study. Conclusions This work demonstrates that a single low-dose of ΔNSsΔNSm vaccine elicits a durable humoral and cellular immune response that persists over months and protects C57BL/6 mice against lethal RVF disease.