SYSTEMS ANALYSIS OF ADULT AND PEDIATRIC RESPONSES TO THE VSV-ZEBOV EBOLA VACCINE - Sofia ref.: 116068

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The vesicular stomatitis virus (VSV)-Zaire Ebola vaccine (VSV-ZEBOV) is a recombinant vector-based vaccine in which the VSV envelope glycoprotein was replaced with the Zaire strain Ebola virus glycoprotein. Within one year of the initiation of its clinical development, the VSV-ZEBOV vaccine has demonstrated safety, immunogenicity and a remarkably high protective efficacy against Ebola Virus Disease, using a high vaccine dose (2x107 pfu) in the WHO-sponsored VSV-ZEBOV ring-vaccination trial in adults in Guinea. However, several key questions remain unanswered, including its mode of action, its correlation with protection and reactogenicity, the expected duration of protective efficacy and determinants of long-term responses, the influence of baseline immunity on vaccine “take”, and the vaccine efficacy in children - a most vulnerable population. Following the interruption of the 2014-2015 Ebola Virus Disease (EVD) outbreak, these questions, being central to the future licensing and use of VSV-ZEBOV, may not be addressed by collecting field data. The VSV-EBOPLUS project therefore proposes to use cutting-edge systems biology approaches to address these key questions, capitalizing on the unique availability of large series of extremely well defined samples from clinical vaccine studies with the VSV-ZEBOV vaccine in three different continents (Europe, Africa, US). Specifically, the overarching objective of VSV-EBOPLUS is to comprehensively decipher the immune and molecular signatures of adult and pediatric responses elicited by VSV-ZEBOV through systems biology approaches. VSV-EBOPLUS will benefit from harmonized and standardized clinical trial protocols, in almost 1’000 adults, adolescents and children. We propose: 1) to examine early (days 0 to 7) blood samples from 512 adults injected with graded doses (from 3x103 to 1x108 pfu) of VSV-ZEBOV;