Correlates of vaccine-induced protective immunity against Ebola virus disease

Ebola virus disease is a deadly infection which occurs in sporadic outbreaks. Several vaccine candidates have been developed. The most advanced candidate is the recombinant VSV Delta G-ZEBOV-GP vaccine, in which the Vesicular Stomatitis Virus (VSV) envelope glycoprotein is replaced by the Zaire strain Ebola virus (ZEBOV) glycoprotein (GP). This vaccine demonstrated 100% protection in a ring vaccination trial performed in Guinea in 2015, was granted "Breakthrough Therapy Designation" by the FDA and PRIority Medicines (PRIME), and is currently (June 2018) used to support outbreak control in Democratic Republic of Congo. rVSV Delta G-ZEBOV-GP elicits a strong and durable antibody response in most vaccinees. This sustained Ebola GP-specific antibody response correlates with an early activation of innate immunity, especially of monocytes and of type-I interferon induced genes. Despite significant progress in the characterization of vaccine-induced immunity, human correlates of protection against Ebolavirus infection have not yet been fully established. A systems biology approach, integrating clinical, immunological, transcriptomic and metabolomic data from pre-clinical and clinical vaccine studies, together with data from disease survivors, will be instrumental to identify Ebola vaccine correlates of protection. The information generated for the rVSV Delta G-ZEBOV-GP vaccine may also help identify the correlates of protection of the other Ebola vaccine candidates.