Vector induced humoral responses after rVSVΔG-ZEBOV-GP immunization identify vaccinated individuals and correlate with Ebola virus glycoprotein antibodies

Abstract

Background The robustness and persistence of vaccine antigen-induced antibodies are often used as proxy indicators of vaccine efficacy, but immune responses to vaccine vectors are typically less well-defined. Our study considered the kinetics of immunoglobulin (IgG) responses against the vector (vesicular stomatitis Indiana virus [VSIV]) nucleoprotein (N) and the inserted antigen (Ebola virus [EBOV]) glycoprotein (GP1,2) components of the rVSVΔG-ZEBOV-GP (rVSV-ZEBOV) vaccine and evaluated their use as biomarkers to confirm self-reported vaccination status. Methods From the Partnership for Research on Ebola Virus in Liberia (PREVAIL) I clinical trial (NCT02344407), we randomly selected 212 participants who received rVSV-ZEBOV (n=107) or placebo (n=105). Levels of IgG antibodies to EBOV GP1,2 or VSIV N were measured using the Filovirus Animal Non-Clinical Group (FANG) ELISA and a newly developed single-molecule array (Simoa) immunoassay, respectively. Results Anti-EBOV GP1,2 IgG and anti-VSIV N IgG were first detected 10–14 d post-vaccination, further increased at 28 d, and remained stable through 360 d. Antibody titers were significantly higher in women compared to men. Anti-EBOV GP1,2 and anti-VSIV N IgG titers were significantly correlated (p<0.001) at 28 d (r=0.47), 180 d (r=0.45), and 360 d (r=0.59). At 28 d, the area under the curve (AUC) of receiver operating characteristic (ROC) curves discriminated vaccinated from unvaccinated patients with high accuracy (AUC=0.965 for anti-VSIV N IgG; AUC=0.945 for anti-EBOV GP1,2 IgG [p<0.001]). Conclusions We report a reliable assay to measure vector-induced humoral responses after rVSV-ZEBOV vaccination and demonstrate the assay’s utility to confirm vaccination status.