Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults.

Background. This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV Delta G-ZEBOV-GP). Methods. Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSV Delta G-ZEBOV-GP (2 x 10(7) plaque-forming units [pfu]), high-dose 1 x 10(8) pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. Post hoc analysis of risk factors associated with arthritis following vaccination was performed. Results. ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSV Delta G-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSV Delta G-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, >= 94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, >= 2-fold increase, titer >= 200 EU/mL), with responses persisting at 24 months in >= 91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination. Conclusions. Immune responses to rVSV Delta G-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSV Delta G-ZEBOV-GP development.