Questions remain concerning the safety, durability and kinetics of immune responses, particularly in children, for vaccines that have been used to prevent Ebola virus disease (EVD).
A randomized, double-blind, phase 2 trial was conducted in West Africa to compare the safety and immunogenicity of three vaccine strategies against EVD with placebo: the Ad26.ZEBOV vaccine followed by the MVA-BN-Filo vaccine (Ad26/MVA) given at 56 days, and the rVSV?G-ZEBOV-GP vaccine (rVSV) given without an rVSV?G-ZEBOV-GP boost or with boost (rVSVB) at 56 days. IgG antibody concentrations were measured at baseline, at days 7, 14, 28, 56, and 63, and at months 3, 6, and 12. The primary immunogenicity endpoint was assessed at month 12; antibody responders were defined as participants with both a 4-fold increase or greater from baseline and an antibody concentration? 200 EU/mL.
1,400 adults and 1,401 children were randomized to receive Ad26/MVA, rVSV, rVSVB, or placebo. The median (25th, 75th percentiles) age of adult participants was 27 (20, 38) years; 45% were female. One-third of children were enrolled in each of the age groups 1-4, 5-11, and 12-17 years, and 46% were female. Compared to placebo, both adults and children in the vaccination groups reported more injection site reactions and symptoms, almost exclusively of low-grade severity, in the week following the prime and second (MVA) or booster (rVSV) vaccinations. These differences were not seen at subsequent follow-up visits. Serious adverse events were uncommon and did not differ significantly between the vaccine groups and the placebo group. The percentages of antibody responders among adults and children at month 12 were 41% and 79%, respectively, for Ad26/MVA, 76% and 87% for rVSV, 81% and 93% for rVSVB, and 2.7% and 3.6% for placebo (p<0.001 for all comparisons with placebo). Significant differences (p<0.001) in the percentage of antibody responders between each vaccine group and placebo were evident by day 14.
Both adults and children evidenced significant immune responses to the three Ebola vaccine strategies at month 12. Side effects were generally mild and moderate and were time-limited for each vaccine for both children and adults.