Vector-Induced Humoral Responses After rVSVΔG-ZEBOV-GP Immunization Identify Vaccinated Individuals and Correlate With Ebola Virus Glycoprotein Antibodies

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BACKGROUND: While vaccine antigen-induced antibodies are often used as proxies for vaccine efficacy, immune responses to vaccine vectors are less well-defined. We describe 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 rVSV-ZEBOV vaccine and evaluate their use as biomarkers to confirm self-reported vaccination status. METHODS: We selected 212 participants randomized to rVSV-ZEBOV (n = 107) or placebo (n = 105). Levels of IgG antibodies to EBOV GP1,2 or VSIV N were measured using an enzyme-linked immunosorbent assay and a newly developed single-molecule array (Simoa) immunoassay, respectively. RESULTS: Anti-EBOV GP1,2 and anti-VSIV N IgG were first detected 10-14 days postvaccination, further increased at 28 days, and remained stable through 360 days. Antibody titers were significantly correlated (P < 0.001) at 28 days (r = 0.47), 180 days (r = 0.45), and 360 days (r = 0.59). At 28 days, the area under the receiver operating characteristic curve (AUC) 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.

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