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A dose-dependent pl...
A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa
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Huttner, A. (author)
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Combescure, C. (author)
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Grillet, S. (author)
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Haks, M. C. (author)
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Quinten, E. (author)
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Modoux, C. (author)
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Agnandji, S. T. (author)
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Brosnahan, J. (author)
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Dayer, J. A. (author)
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- Harandi, Ali M, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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Kaiser, L. (author)
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Medaglini, D. (author)
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Monath, T. (author)
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Roux-Lombard, P. (author)
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Kremsner, P. G. (author)
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Ottenhoff, T. H. M. (author)
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Siegrist, C. A. (author)
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2017
- 2017
- English.
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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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https://europepmc.or...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- vesicular stomatitis-virus
- monocyte chemoattractant protein-1
- yellow-fever vaccine
- receptor antagonist
- double-blind
- randomized-trial
- systems biology
- open-label
- immunity
- infection
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Huttner, A.
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Combescure, C.
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Grillet, S.
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Haks, M. C.
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Quinten, E.
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Modoux, C.
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show more...
-
Agnandji, S. T.
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Brosnahan, J.
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Dayer, J. A.
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Harandi, Ali M, ...
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Kaiser, L.
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Medaglini, D.
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Monath, T.
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Roux-Lombard, P.
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Kremsner, P. G.
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Ottenhoff, T. H. ...
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Siegrist, C. A.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Science Translat ...
- By the university
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University of Gothenburg