Dataset Information

Limited benefit of post-exposure prophylaxis with VSV-EBOV in Ebola virus-infected rhesus macaques.

ABSTRACT: VSV-EBOV has been successfully used in ring vaccination approaches during Ebola virus (EBOV) disease outbreaks demonstrating its general benefit in short-term prophylactic vaccination, but actual proof of its benefit in true post-exposure prophylaxis (PEP) for humans is missing. Animal studies have indicated PEP efficacy when VSV-EBOV was used within hours of lethal EBOV challenge. Here, we used a lower EBOV challenge dose and a combined intravenous and intramuscular VSV-EBOV administration to improve PEP efficacy in the rhesus macaque model. VSV-EBOV treatment 1 hour post EBOV challenge resulted in delayed disease progression but little benefit in outcome. Thus, we could not confirm previous results indicating questionable benefit of VSV-EBOV for EBOV PEP even in a nonhuman primate model.

SUBMITTER: Bushmaker T

PROVIDER: S-EPMC10651186 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Limited Benefit of Postexposure Prophylaxis With VSV-EBOV in Ebola Virus-Infected Rhesus Macaques.

Bushmaker Trenton T Feldmann Friederike F Lovaglio Jamie J Saturday Greg G Griffin Amanda J AJ O'Donnell Kyle L KL Strong James E JE Sprecher Armand A Kobinger Gary G Geisbert Thomas W TW Marzi Andrea A Feldmann Heinz H

The Journal of infectious diseases 20231101 Suppl 7

Vesicular stomatitis virus-Ebola virus (VSV-EBOV) vaccine has been successfully used in ring vaccination approaches during EBOV disease outbreaks demonstrating its general benefit in short-term prophylactic vaccination, but actual proof of its benefit in true postexposure prophylaxis (PEP) for humans is missing. Animal studies have indicated PEP efficacy when VSV-EBOV was used within hours of lethal EBOV challenge. Here, we used a lower EBOV challenge dose and a combined intravenous and intramus ...[more]

PMID: 37474155

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Project description:Ebola virus (EBOV), of the family Filoviridae, is an RNA virus that can cause a hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes that have been observed during multiple RNA virus infections, including in vitro EBOV infection, and have previously been associated with viral persistence and immunostimulatory activity. As DVGs have been detected in cells persistently infected with EBOV, we hypothesized that DVGs may also accumulate during viral replication in filovirus-infected hosts. Therefore, we interrogated sequence data from serum and tissue samples using a bioinformatics tool in order to identify the presence of DVGs in nonhuman primates (NHPs) infected with EBOV, Sudan virus (SUDV), or Marburg virus (MARV). Multiple 5' copy-back DVGs (cbDVGs) were detected in NHP serum during the acute phase of filovirus infection. While the relative abundance of total DVGs in most animals was low, serum collected during acute EBOV and SUDV infections, but not MARV infections, contained a higher proportion of short trailer sequence cbDVGs than the challenge stock. This indicated an accumulation of these DVGs throughout infection, potentially due to the preferential replication of short DVGs over the longer viral genome. Using reverse transcriptase PCR (RT-PCR) and deep sequencing, we also confirmed the presence of 5' cbDVGs in EBOV-infected NHP testes, which is of interest due to EBOV persistence in semen of male survivors of infection. This work suggests that DVGs play a role in EBOV infection in vivo and that further study will lead to a better understanding of EBOV pathogenesis. IMPORTANCE The study of filovirus pathogenesis is critical for understanding the consequences of infection and for the development of strategies to ameliorate future outbreaks. Defective viral genomes (DVGs) have been detected during EBOV infections in vitro; however, their presence in in vivo infections remains unknown. In this study, DVGs were detected in samples collected from EBOV- and SUDV-infected nonhuman primates (NHPs). The accumulation of these DVGs in the trailer region of the genome during infection indicates a potential role in EBOV and SUDV pathogenesis. In particular, the presence of DVGs in the testes of infected NHPs requires further investigation as it may be linked to the establishment of persistence.

Dataset Information

Limited benefit of post-exposure prophylaxis with VSV-EBOV in Ebola virus-infected rhesus macaques.

Publications

Limited Benefit of Postexposure Prophylaxis With VSV-EBOV in Ebola Virus-Infected Rhesus Macaques.

Similar Datasets

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