Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV
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Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV. / Friedrich, Sarah-Kim; Schmitz, Rosa; Bergerhausen, Michael; Lang, Judith; Cham, Lamin B; Duhan, Vikas; Häussinger, Dieter; Hardt, Cornelia; Addo, Marylyn; Prinz, Marco; Asano, Kenichi; Lang, Philipp Alexander; Lang, Karl Sebastian.
in: VACCINES-BASEL, Jahrgang 8, Nr. 1, 23.03.2020.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV
AU - Friedrich, Sarah-Kim
AU - Schmitz, Rosa
AU - Bergerhausen, Michael
AU - Lang, Judith
AU - Cham, Lamin B
AU - Duhan, Vikas
AU - Häussinger, Dieter
AU - Hardt, Cornelia
AU - Addo, Marylyn
AU - Prinz, Marco
AU - Asano, Kenichi
AU - Lang, Philipp Alexander
AU - Lang, Karl Sebastian
PY - 2020/3/23
Y1 - 2020/3/23
N2 - 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 Usp18 in CD169+ macrophages is one important factor modulating the anti-Ebola virus immune response. The absence of Usp18 in CD169+ macrophages led to the reduced local replication of VSV-EBOV followed by a diminished innate as well as adaptive immune response. In line, CD169-Cre+/ki x Usp18fl/fl mice showed reduced innate and adaptive immune responses against the VSV wildtype strain and died quickly after infection, suggesting that a lack of Usp18 makes mice more susceptible to the side effects of the VSV vector. In conclusion, our study shows that Usp18 expression in CD169+ macrophages is one important surrogate marker for effective vaccination against VSV-EBOV, and probably other VSV-based vaccines also.
AB - 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 Usp18 in CD169+ macrophages is one important factor modulating the anti-Ebola virus immune response. The absence of Usp18 in CD169+ macrophages led to the reduced local replication of VSV-EBOV followed by a diminished innate as well as adaptive immune response. In line, CD169-Cre+/ki x Usp18fl/fl mice showed reduced innate and adaptive immune responses against the VSV wildtype strain and died quickly after infection, suggesting that a lack of Usp18 makes mice more susceptible to the side effects of the VSV vector. In conclusion, our study shows that Usp18 expression in CD169+ macrophages is one important surrogate marker for effective vaccination against VSV-EBOV, and probably other VSV-based vaccines also.
U2 - 10.3390/vaccines8010142
DO - 10.3390/vaccines8010142
M3 - SCORING: Journal article
C2 - 32210083
VL - 8
JO - VACCINES-BASEL
JF - VACCINES-BASEL
SN - 2076-393X
IS - 1
ER -