In vitro cellular tropism and immunomodulatory response to rVSVΔG-ZEBOV-GP in human cells derived from tissues associated with adverse events

Our study expanded knowledge about the cellular tropism of rVSVΔG-ZEBOV-GP vaccine toward peripheral blood mononuclear cells and cell lines derived from tissues (skin, vessels, and joints) associated with unexpected AEs, as well as their possible contribution to the vaccine-induced innate response. Using in vitro infection and co-culture techniques, we showed that rVSVΔG-ZEBOV-GP-infected monocytes can transmit the virus to synoviocytes, and how infection affects human monocytes and synoviocytes at the protein and transcriptomic levels. Our findings provide insights into the in vitro off-target infection dynamics and innate immune response triggered by rVSVΔG-ZEBOV-GP vaccine. While these results may enhance understanding of rVSV-based vectors, in vivo relevance remains unclear, as does whether the effects come from the VSV backbone or Ebola GP. These findings support the evaluation of off-target effects of rVSV-based vaccine candidates, including those under development for hemorrhagic fever viruses, such as Marburg virus, Sudan virus, and Lassa virus, especially if similar AEs are observed.