Immunogenicity and Vaccine Shedding after 1 or 2 Doses of Rvsvδg-Zebov-gp Ebola Vaccine (ERVEBO®): Results from a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults.

Background The rVSV Delta G-ZEBOV-GP vaccine (ERVEBO (R)) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older.Methods The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSV Delta G-ZEBOV-GP, 2-dose rVSV Delta G-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR.Results In total, 819 children and 783 adults were randomized to receive rVSV Delta G-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSV Delta G-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSV Delta G-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2.Conclusions A single dose of rVSV Delta G-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSV Delta G-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18).Conclusions A single dose of rVSV Delta G-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSV Delta G-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18). A single dose of rVSV Delta G-ZEBOV-GP induced robust antibody responses in adults and children. Vaccine shedding occurred in 31.7% of children, peaking by Day 7. No shedding was observed after Day 28 post-dose 1 or after a second dose of rVSV Delta G-ZEBOV-GP.