Ebola Vaccines

Inserm, NIH, LSHTM

Yazdan Yazdanpanah MD, PhD-AP-HP

Randomized clinical trial evaluating 3 Ebola vaccines strategies in Adult and Children in four African countries. Participants will be seen for a year (with a total of 9 visits) to compare each of the three vaccine strategies with the pooled placebo group (protocols v2.0 to v4.0) and for 4 additional years (1 visit per year) to assess the long-term durability of the antibody response (protocols v5.0 to v7.0). The safety will be assessed over the 5 five years. Following the new Ebola outbreak declared in Guinea in February 2021, and the recent vaccine licensures, the participants who received the placebo will be vaccinated with a single dose of rVSVΔG-ZEBOV-GP vaccine in Liberia and Mali and with the Ad26.ZEBOV/MVA-BN-Filo vaccine strategy in Guinea and Sierra Leone. The participants who received an incomplete Ad26.ZEBOV/MVA-BN-Filo vaccine strategy will be offered a single dose of the Ad26.ZEBOV or MVA-BN-Filo vaccine in Guinea and Sierra Leone and a single dose of rVSVΔG-ZEBOV-GP in Liberia and Mali.

Randomized, double-blind, placebo-controlled trial of three vaccine strategies

To compare each of the three vaccine strategies with the pooled placebo group (3 pair-wise comparisons) for antibody response 12 months after randomization (prime vaccination).

The primary immunogenicity endpoint is the GP-EBOV antibody response 12 months after randomization. This endpoint will be used to compare the immunogenicity of the three vaccine strategies with placebo. The primary analysis for adults and children will be performed for participants who do not have elevated antibody levels at baseline.

Adults and children, aged at least 1 year of age, were invited to participate.

Protocol version 4.0, participants were randomized to the following 5 groups in a 2:1:2:1:1 allocation 1) Ad26.ZEBOV (prime) (0.5 mL) followed by an MVA-BN-Filo boost (0.5 mL) at 56 days; 2) placebo (prime and boost at 56 days) (0.5 mL); 3) rVSVΔG-ZEBOV-GP (prime) (1 mL) followed by placebo boost (1 mL) at 56 days; 4) rVSVΔG-ZEBOV-GP (prime) (1 mL) followed by rVSVΔG-ZEBOV-GP boost (1 mL) at 56 days; and 5) placebo (prime and boost at 56 days) (1 mL) (Figure 1). At 56 days, participants assigned to the rVSVΔG-ZEBOV-GP vaccine without a boost and the two placebo groups received a placebo vaccination. Those initially given the Ad26.ZEBOV vaccine received the MVA-BN-Filo vaccine at 56 days. Those assigned to the boosted rVSVΔG-ZEBOV-GP arm received a booster vaccination with the rVSVΔG-ZEBOV-GP vaccine at 56 days.

4,789 participants

The trial is conducted in Guinea, Liberia, Mali, and Sierra Leone.

Participants were seen at frequent follow-up visits for 12 months. After the 12 months of follow-up is complete for all participants, the study was unblinded and all participants are currently being seen annually through 60 months.

Supported in part by the NIH, by INSERM, and by the LSHTM. Janssen and Merck Sharp and Dohme provided the vaccines according to the EBOVAC 1 grant agreement. This project is part of the EDCTP 2 program supported by the EU (grant number,RIA2017S-2014–PREVAC-UP). This project received funding from the IMI 2 Joint Undertaking (grant number, 115854), which receives support from the EU Horizon 2020 Research and Innovation Program and the European Federation of Pharmaceutical Industries and Associations. Funding was provided in part by the NCI (grant number, HHSN261201500003I) through the FNLCR and BARDA (grant number, HHS0100201700012C). The project has been funded by a dedicated INSERM allocation on behalf of the French Research Ministry.

Methodological aspects, trial coordination, datamanagement, statistical analysis and monitoring coordination

https://clinicaltrials.gov/ct2/show/NCT02876328