Antiviral Innate Responses Induced by VSV-EBOV Vaccination Contribute to Rapid Protection

Ebola virus (EBOV) is a single-stranded RNA virus that causes Ebola virus disease (EVD) characterized by excessive inflammation, lymphocyte apoptosis, hemorrhage, and coagulation defects leading to multiorgan failure and shock. Recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (VSV-EBOV), which is highly efficacious against lethal challenge in nonhuman primates, is the only vaccine that successfully completed a phase III clinical trial. Additional studies showed VSV-EBOV provides complete and partial protection to macaques immunized 7 and 3 days before EBOV challenge, respectively. However, the mechanisms by which this live-attenuated vaccine elicits rapid protection are only partially understood. To address this, we carried out a longitudinal transcriptome analysis of host responses in whole blood samples collected from cynomolgus macaques vaccinated with VSV-EBOV 28, 21, 14, 7 and 3 days before EBOV challenge. Our findings indicate the transcriptional response to the vaccine peaks 7 days following vaccination and contains signatures of both innate antiviral immunity as well as B-cell activation. EBOV challenge 1 week after vaccination resulted in large gene expression changes suggestive of a recall adaptive immune response 14 days post-challenge. Lastly, the timing and magnitude of innate immunity and interferon stimulated gene expression correlated with viral burden and disease outcome in animals vaccinated 3 days before challenge.