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Abstract

Sudan virus (SUDV) has caused multiple outbreaks of human disease with case fatality rates ranging from 41 to 100%. We have previously shown that a single vaccination with a recombinant vesicular stomatitis virus-based vaccine expressing the SUDV-Gulu glycoprotein (VSV-SUDV) prevented clinical and fatal disease from lethal SUDV challenge in cynomolgus macaques. With the high probability of future outbreaks, it is critical to determine the molecular mechanisms of VSV-SUDV-mediated protection and the ability to impart rapid protection against SUDV infection. In this study, RNA from whole blood samples obtained from nine cynomolgus macaques that were challenged with SUDV-Gulu post-vaccination with either VSV-EBOV (28 days before challenge, n = 3) or VSV-SUDV (28 or 7 days before challenge, n = 3/group) was subjected to bulk RNA sequencing. EdgeR, STEM, MaSigPro, and CIBERSORTx were used to assess longitudinal transcriptional changes elicited by vaccination and challenge. Our analysis revealed that VSV-SUDV and VSV-EBOV elicited distinct transcriptional responses. Moreover, NHPs vaccinated with VSV-EBOV (non-protective) generated a transcriptional response following SUDV challenge indicative of dysregulated inflammation. In contrast, NHPs that received VSV-SUDV vaccine generated a transcriptional response indicative of a recall adaptive immune response. Finally, in-silico deconvolution methods indicated changes in immune cell frequency consistent with immune response and resolution in the VSV-SUDV-vaccinated NHPs that are not observed with VSV-EBOV-vaccinated NHPs. These data indicate that VSV-SUDV vaccination results in a protective humoral response as late as 7 days before challenge despite transcriptional evidence of subclinical features of infection.

Document Type

Article

Publication Date

2026

Notes/Citation Information

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Digital Object Identifier (DOI)

https://doi.org/10.1371/journal.ppat.1014143

Funding Information

This study was funded by the Intramural Research Program, NIAID, NIH (A.M.) and research award from the University of Kentucky (I.M). The contributions of the NIH author were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the author and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. A.M. received salary from NIH.

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