| Summary: | Ebola virus epidemics can be effectively limited by the VSV-EBOV vaccine (Ervebo) due to its rapid protection abilities; however, side effects prevent the broad use of VSV-EBOV as vaccine. Mechanisms explaining the efficient immune activation after single injection with the VSV-EBOV vaccine remain mainly unknown. Here, using the clinically available VSV-EBOV vaccine (Ervebo), we show that the cell-intrinsic expression of the interferon-inhibitor <i>Usp18</i> in CD169<sup>+</sup> macrophages is one important factor modulating the anti-Ebola virus immune response. The absence of <i>Usp18</i> in CD169<sup>+</sup> macrophages led to the reduced local replication of VSV-EBOV followed by a diminished innate as well as adaptive immune response. In line, <i>CD169</i>-Cre<sup>+/ki</sup> x <i>Usp18</i><sup>fl/fl</sup> mice showed reduced innate and adaptive immune responses against the VSV wildtype strain and died quickly after infection, suggesting that a lack of <i>Usp18</i> makes mice more susceptible to the side effects of the VSV vector. In conclusion, our study shows that <i>Usp18</i> expression in CD169<sup>+</sup> macrophages is one important surrogate marker for effective vaccination against VSV-EBOV, and probably other VSV-based vaccines also.
|
|---|