The overall objective of VSV-EBOPLUS is to comprehensively decipher, using systems biology approaches, the immune and molecular signatures of the human response elicited in adults and children by the highly protective vesicular stomatitis virus (VSV)‐vectored Zaire Ebola vaccine (rVSVrG-ZEBOV-GP), which was developed by Public Health Canada (BPSC1001), licensed to NewLink Genetics and subsequently to Merck for further development. Among prophylactic Ebola vaccine candidates, the VSV-ZEBOV vaccine has shown to be reactogenic but safe, immunogenic and protective in human studies. VSV-ZEBOV is a recombinant VSV vector in which the VSV envelope glycoprotein was replaced with the Zaire strain Ebola virus glycoprotein (ZEBOV-GP), giving rise to rVSVΔG-ZEBOV-GP.
In the VSV-EBOPLUS project, it will be characterized responses from VSV-ZEBOV phase I/Ib/II clinical trials including (i) dose-ranging, (ii) a pediatric cohort, and (iii) long-term follow-up studies.
VSV-EBOPLUS represents a unique effort to promote and translate rVSVrG-ZEBOV-GP vaccine development, by in depth profiling of human adult and pediatric responses to vaccination in relation to safety, vaccine dose and long-term immunity.
Building upon the seminal emerging findings, the availability of large numbers of samples from vaccines across different age groups, time points and continents from new clinical trials and the opportunity to study a vaccine that induces an outstanding protective efficacy against Ebola virus disease (EVD), VSV-EBOPLUS will harness state-of-the-art and cutting edge technologies and systems biology approaches to comprehensively study the immune and molecular signatures of the human response elicited by the highly protective VSV-ZEBOV vaccine. The results obtained from this project will inform the development, and use, of a safe and efficacious vaccine to counter Ebola infection.
The VSV-EBOPLUS project builds upon and significantly extends the objectives of the VSV-EBOVAC project (www.vsv-ebovac.eu), by applying cutting edge metabolomics, immunomics, transcriptomics, miRNomics, and systems vaccinology approaches to provide key information for Ebola vaccine R&D in particular, and human vaccines in general.
VSV-EBOPLUS Specific Objectives:
- Characterize the innate and adaptive immune responses elicited by various doses of rVSVrG-ZEBOV-GP vaccine in adults and children in clinical trials conducted in Switzerland, Gabon and USA
- Assess the dynamic of the metabolomics and immunologic profiles to define how they correlate to vaccine reactogenicity, antibody responses and viral control
- Identify the contribution of specific cells to rVSVrG-ZEBOV-GP -induced innate responses
- Determine the dynamic transcriptomic profiles of adult and pediatric responses to rVSVrG-ZEBOV-GP vaccination at multiple time points
- Generate / exploit the clinical safety / reactogenicity and the immunology (metabolomics, immunomics, and transcriptomics) databases for integrative analysis