<i>In vitro</i> 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 <i>in vitro</i> 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 <i>in vitro</i> off-target infection dynamics and innate immune response triggered by rVSVΔG-ZEBOV-GP vaccine. While these results may enhance understanding of rVSV-based vectors, <i>in vivo</i> 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.