Predicting and achieving vaccine efficacy remains a major challenge. Here, Rechtien et al used a systems vaccinology approach to disentangle the early innate immune responses elicited by the Ebola vaccine rVSV-Zaire Ebola virus (ZEBOV) to identify innate immune responses correlating with Ebola virus (EBOV)-glycoprotein (GP)-specific antibody induction. Of note, this replication-competent recombinant vaccine candidate is based on the vesicular stomatitis virus (rVSV)-based vaccine vector, which has been shown safe and immunogenic in a number of phase I trials.
The vaccine rVSV-ZEBOV induced a rapid and robust increase in cytokine levels, with a maximum peak at day 1, especially for CXCL10, MCP-1 and MIP-1β. Assessment of PBMCs revealed significant induction of co-stimulatory molecules, monocyte/DC activation and NK cell activation at day 1 post-vaccination. The expression of these molecules begin to decline at day 3.
Interestingly, CXCL10 plasma levels and frequency of activated NK cells at day 3 were found to be positively correlated with antibody responses. CD86+ expression in monocytes and mDCs at day 3 are negatively correlated with antibody responses (See figure on top).
The most number of upregulated genes were detected at day 1 post-vaccination. Critically, the early gene signature linked to CXCL10 pathway, including TIFA (TRAF-interacting protein with forkhead-associated domain) on day 1, SLC6A9 (solute carrier family 6 member 9) on day 3, NFKB1 and NFKB2 were most predictive of antibody responses.
Data is stored under NCBI GEO: GSE97590.