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- Huttner, A., et al.
(author)
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A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa
- 2017
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 9:385
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Journal article (peer-reviewed)abstract
- The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1 beta/CCL4, IL-6, TNF-alpha, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variabilitywas identified. Its score was higher in HD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees who subsequently developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose did not influence the signature despite its influence on specific outcomes. The Geneva-derived signature associated strongly (rho = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambarene, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambarene HD vaccinees, none of whom experienced arthritis. This signature, which reveals monocytes' critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines.
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4. |
- Vianello, Eleonora, et al.
(author)
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Global blood miRNA profiling unravels early signatures of immunogenicity of Ebola vaccine rVSVΔG-ZEBOV-GP
- 2023
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In: iScience. - 2589-0042. ; 26:12
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Journal article (peer-reviewed)abstract
- The vectored Ebola vaccine rVSVΔG-ZEBOV-GP elicits protection against Ebola Virus Disease (EVD). In a study of forty-eight healthy adult volunteers who received either the rVSVΔG-ZEBOV-GP vaccine or placebo, we profiled intracellular microRNAs (miRNAs) from whole blood cells (WB) and circulating miRNAs from serum-derived extracellular vesicles (EV) at baseline and longitudinally following vaccination. Further, we identified early miRNA signatures associated with ZEBOV-specific IgG antibody responses at baseline and up to one year post-vaccination, and pinpointed target mRNA transcripts and pathways correlated to miRNAs whose expression was altered after vaccination by using systems biology approaches. Several miRNAs were differentially expressed (DE) and miRNA signatures predicted high or low IgG ZEBOV-specific antibody levels with high classification performance. The top miRNA discriminators were WB-miR-6810, EV-miR-7151-3p, and EV-miR-4426. An eight-miRNA antibody predictive signature was associated with immune-related target mRNAs and pathways. These findings provide valuable insights into early blood biomarkers associated with rVSVΔG-ZEBOV-GP vaccine-induced IgG antibody responses.
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