Host immune responses after a low dose VSV-based vaccine

Infection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in hemorrhagic disease with high case fatality rates in humans. Despite its importance, there are no licensed vaccines or therapeutics that can be deployed in the event of an outbreak. A vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) is currently in clinical development. Previously, a single dose of VSV-MARV administered 5 weeks before lethal MARV challenge conferred uniform protection in nonhuman primates (NHPs). Further inquiry demonstrated the fast-acting potential of VSV-MARV, as NHPs were protected from disease as early as 7 days after vaccination. Establishing the minimum vaccine dose that confers protection is essential for delivering the most beneficial public health outcomes. Our group recently demonstrated that even at a low dose VSV-MARV protected NHPs within 7 days of virus challenge. In this study, we used RNA-sequencing to analyze whole blood samples collected over time from NHPs vaccinated with this low dose of VSV-MARV both 14 and 7 days before lethal MARV challenge. The control group was vaccinated with a similar VSV-based Ebola virus before MARV challenge. NHPs vaccinated 14 days before challenge presented with transcriptional changes consistent with an anti-viral response. Limited gene expression changes were observed in the group vaccinated 7 days before challenge. After challenge, T cell activation, differentiation, and lymphocyte-mediated immunity played a role in protection against MVD in the group vaccinated 14 days before challenge. These changes were not observed in the group vaccinated 7 days before challenge or the control group indicating that the length of time between vaccination and challenge influenced observable significant gene expression changes. Our results indicate that even at a low dose VSV-MARV elicits distinct immune responses that correlate with protection against MVD. A low dose of VSV-MARV remains a viable option to deliver beneficial public health outcomes in the event of future outbreaks.