The overall objective of VSV-EBOVAC is to comprehensively characterize the immune and molecular signatures of immune responses elicited in humans by rVSV-ZEBOV, a promising Ebola vaccine candidate based on the replication-competent recombinant vesicular stomatitis virus (VSV) expressing a Zaire ebolavirus (EBOV) glycoprotein.
rVSV-ZEBOV was selected by the World Health Organization (WHO) as one of the most promising vaccine candidates for further development. To accelerate its clinical development, the WHO initiated a consortium (VEBCON) to support parallel first-in-man Phase I clinical trials in Europe and Africa. Preliminary results have documented that rVSV-ZEBOV is immunogenic albeit reactogenic at high doses. Remarkably, high doses of rVSV-ZEBOV proved highly efficacious in preventing Ebola virus disease within a few days in a Guinea Phase III trial. The VSV-EBOVAC project capitalizes upon this innovative effort by acquiring new and critical in depth knowledge of innate and adaptive immune responses elicited in humans by rVSV-ZEBOV vaccine, with special emphasis on transcriptomic and metabolomic signatures.
VSV-EBOVAC offers an ambitious program using cutting-edge technologies in performing in depth characterization of clinical samples collected longitudinally before and after rVSV-ZEBOV immunization from about 200 volunteers in Switzerland, Gabon and Kenya, and extending the WHO initiated Phase I clinical studies to identify the signatures and determinants of persistent, long-term "memory" immune responses up to 12 months. VSV-EBOVAC thus ensures that the maximum possible information will be "retrieved" from the ongoing rVSV-ZEBOV clinical studies, exploited and shared, to facilitate and enhance knowledge of the vaccine's safety and immunogenicity, thus filling a critical knowledge gap in Ebola vaccine development.
VSV-EBOVAC is a public private consortium of 12 partners involving experts from academic institutions, scientists of the 3 main clinical sites (Switzerland, Gabon, Kenya), the representative from the vaccine manufacturer, a small and medium-sized enterprises (SMEs) and research institutes.
On March 1st 2015 the IMI-JU funded the project VSV-EBOVAC; the total budget of the project is 8 millions of Euros and it will last for three years.
Specific objectives of VSV-EBOVAC:
- Build on and extend up to 12 month the Phase I/II dose-finding randomized, single-center, double-blind, placebo controlled safety and immunogenicity trial of the rVSV-ZEBOV vaccine in healthy adults in Switzerland, Kenya and Gabon
- Characterize the innate and adaptive immune responses elicited by various doses of rVSV-ZEBOV and define how they contribute to vaccine reactogenicity, antibody responses and viral control
- Characterize rVSV-ZEBOV induced humoral immune response
- Perform a direct comparison of the long-term immunity (antibodies, memory B cells, memory CD8 and CD4 T cells) generated in volunteers vaccinated with the rVSV-ZEBOV vaccine compared to individuals that have survived Ebola infection
- Determine the dynamic transcriptomic and metabolomic profiles of the human immune response to VSV-ZEBOV vaccination at multiple time points