Characterization of immune correlates following Rift Valley fever virus infection or vaccination

Rift Valley fever virus (RVFV) is an arbovirus of clinical and agricultural relevance found throughout Africa. Our consortium is currently supported by CEPI to conduct baseline sero-epidemiology studies of RVFV and Phase I/II clinical trials of DDVax, a live attenuated RVFV vaccine in Tanzania. While the primary goals of these trials are clearly safety and immunogenicity, there will be vaccinated and control cohorts in an area that is endemic for RVFV; this provides a unique opportunity to identify exposures/infections as they occur over time in these cohorts and make direct immunologic comparisons between the groups. Longitudinal serum samples from these cohorts will be tested using a series of humoral assays, including virus associated Fc mediated activity assays that our group will develop and optimize. Serum samples from clinical trial participants will be used for dose-down passive transfer studies in relevant animal models to define mechanistic immune correlates of protection from RVFV hepatitis or encephalitis; these data could be useful for immunobridging from animal model protection data to human immunogenicity if needed for licensure. All immunologic and outcome data from human participants and animal studies will be subjected to high-dimensional bioinformatic analysis to identify immunologic correlates of protection from RVFV.