A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa
- 11 April 2017
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 9 (385)
- https://doi.org/10.1126/scitranslmed.aaj1701
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.Keywords
Funding Information
- European Commission Directorate-General for Research and Innovation (award302305, 115842)
This publication has 63 references indexed in Scilit:
- Learning from the Messengers: Innate Sensing of Viruses and Cytokine Regulation of Immunity — Clues for Treatments and VaccinesViruses, 2013
- Acute Reactogenicity after Intramuscular Immunization with Recombinant Vesicular Stomatitis Virus Is Linked to Production of IL-1βPLOS ONE, 2012
- Vesicular Stomatitis Virus–Based Ebola Vaccines With Improved Cross-Protective EfficacyThe Journal of Infectious Diseases, 2011
- Identification of biomarkers for tuberculosis disease using a novel dual-color RT–MLPA assayGenes & Immunity, 2011
- High Prevalence of Both Humoral and Cellular Immunity to Zaire ebolavirus among Rural Populations in GabonPLOS ONE, 2010
- Interaction between Ebola Virus Glycoprotein and Host Toll-Like Receptor 4 Leads to Induction of Proinflammatory Cytokines and SOCS1Journal of Virology, 2010
- Monocyte Chemoattractant Protein-1 (MCP-1): An OverviewJournal of Interferon & Cytokine Research, 2009
- IL‐1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde?FEBS Letters, 2006
- Vesicular stomatitis virus: re-inventing the bulletTrends in Molecular Medicine, 2004
- An index of factorial simplicityPsychometrika, 1974