Usp18 Expression in CD169+ Macrophages is Important for Strong Immune Response after Vaccination with VSV-EBOV.

Sarah-Kim Friedrich,Philipp Alexander Lang,Dieter Häussinger,Karl Sebastian Lang,Vikas Duhan,Rosa Schmitz,Michael Bergerhausen,Cornelia Hardt,Lamin B Cham,Judith Lang,Marco Prinz,Marylyn Addo,Kenichi Asano

doi:10.3390/vaccines8010142

Abstract

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.

Highlights

The Ebola virus (EBOV) is an enveloped, non-segmented negative RNA virus from the family of Filoviruses
As Usp18 modulates Th17 cells and CD11b cells, it remained unknown whether a lack of Usp18 in CD169+ cells contributed to the anti-VSV
VSV replication in inguinal draining lymph nodes was below the detection limit in the absence of Usp18 in CD169+ MΦs compared to WT conditions (Figure 1A)

Summary

Introduction

The Ebola virus (EBOV) is an enveloped, non-segmented negative RNA virus from the family of Filoviruses. It causes hemorrhagic fever in non-human primates and humans [1,2]. EBOV is one of the most pathogenic viruses worldwide, and epidemic outbreaks in the past, such as the Ebola virus outbreak in western Africa from 2013–2016, have demonstrated an urgent need for new vaccines in order to protect the human population. VSV-EBOV (rVSV-EBOV, Ervebo) is among the most powerful newly developed VSV vector vaccines; demonstrating safety and efficacy in clinical studies, and was recently approved by the EMA [3,4,5,6,7]. Ervebo induces rapid protection after vaccination and shows its potential post-exposure efficacy [5]. The mechanisms which explain the effectiveness of the antiviral immune activation are basically unknown

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Discussion

Conclusion