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Scientific article
Open access
English

Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine

Published inVaccines, vol. 9, no. 2, 67
Publication date2021-01-20
First online date2021-01-20
Abstract

Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo®), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. A global transcriptomic approach was used to profile the blood host-response in 51 healthy volunteers enrolled in a phase 1/2 clinical trial. Signatures of the host responses were investigated assessing the enrichment in differentially expressed genes (DEGs) of specific "blood transcription modules" (BTM). Comparison of gene-expression levels showed that vaccination produces a peak of 5469 DEGs at day one, representing 38.6% of the expressed genes. Out of 346 BTMs, 144 were significantly affected by vaccination. Innate immunity pathways were induced from day 1 to day 14. At days 2 and 3, neutrophil modules were downregulated and complement-related modules upregulated. T-cell and cell-cycle associated modules were upregulated at days 7 and 14, while at day 28, no modules remained activated. At day 14, a direct correlation was observed between ZEBOV glycoprotein-specific antibody titres and activation of seven BTMs, including two related to B-cell activation and B cell receptor signalling. Transcriptomic analysis identified an rVSVΔG-ZEBOV-GP-induced signature and demonstrated a direct correlation of blood transcriptomic changes with ZEBOV glycoprotein-specific antibody titres.

eng
Keywords
  • Ebolavirus Disease
  • VSV-ZEBOV
  • Live viral vector
  • Recombinant VSV
  • Transcriptomics
  • Vaccine
Funding
  • Innovative Medicines Initiative - [115842]
  • Innovative Medicines Initiative - [116068]
Citation (ISO format)
SANTORO, Francesco et al. Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine. In: Vaccines, 2021, vol. 9, n° 2, p. 67. doi: 10.3390/vaccines9020067
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Identifiers
ISSN of the journal2076-393X
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Technical informations

Creation04/06/2022 4:36:00 AM
First validation04/06/2022 4:36:00 AM
Update time03/16/2023 8:40:05 AM
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