Science Translational Medicine, 12 April 2017 Vol 9, Issue 385

Science Translational Medicine
12 April 2017  Vol 9, Issue 385
http://stm.sciencemag.org/
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Focus
Engagement of the medical-technology sector with society
By David Williams, Elazer R. Edelman, Milica Radisic, Cato Laurencin, Darrel Untereker
Science Translational Medicine12 Apr 2017 Full Access
The medical-technology sector must educate society in an unbiased rational way about the successes and benefits of biotechnology innovation.

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A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa
By Angela Huttner, Christophe Combescure, Stéphane Grillet, Mariëlle C. Haks, Edwin Quinten, Christine Modoux, Selidji Todagbe Agnandji, Jessica Brosnahan, Julie-Anne Dayer, Ali M. Harandi, Laurent Kaiser, Donata Medaglini, Tom Monath, VEBCON and VSV-EBOVAC Consortia, Pascale Roux-Lombard, Peter G. Kremsner, Tom H. M. Ottenhoff, Claire-Anne Siegrist
Science Translational Medicine12 Apr 2017 Restricted Access
A specific plasma signature reveals the critical role of monocytes in the VSV-vectored Ebola vaccine immunogenicity and safety.
Monocytes make their mark in Ebola vaccination
A VSV-vectored Ebola vaccine was used in Guinea during the recent outbreak and has now been shown to be incredibly effective in preventing infection. However, the vaccine itself did cause somewhat severe reactions in some subjects, including fever and arthritis. Huttner et al. examined longitudinal plasma samples from vaccine recipients in Europe and Africa to identify a signature of the immune response and adverse events. The signature of monocyte-derived cytokines held true in both cohorts, suggesting that it could also be applied to other vaccine trials to determine immunogenicity and reactogenicity.
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-1β/CCL4, IL-6, TNF-α, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variability was 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 (ρ = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambaréné, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambaréné 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.