Long-term Immunogenicity and Booster Response in Ebola Vaccine Regimen


Phase 2 study of healthcare workers' safety in high-risk populations.

Healthcare worker with Ebola vaccine | Image credits: Unsplash

The long-term immunogenicity of Ebola’s Ad26.ZEBOV, MVA-BN-Filo vaccine regimen and the safety of and immune memory response to an Ad26.ZEBOV booster vaccination at 1 year or 2 years after the initial dose in this population that is at risk. Participants who received a booster 1 year and 2 years after the initial dose exhibited a comparable and strong humoral immune response, endorsing the regimen's use and the adaptable timing for booster administration in prophylactic vaccination for at risk populations.

Between December 18, 2019, and February 8, 2020, 699 healthcare workers and frontline staff were enrolled, but only 698 were divided into 2 groups for analysis, 350 in group 1 and 348 in group 2. Initial Ebola virus glycoprotein-specific IgG binding antibody levels before the booster showed Geometric Mean Concentrations (GMCs) of 279.9 ELISA units (EU) per mL for group 1 and 274.6 EU/mL for group 2, increasing approximately 5 times from baseline levels for both groups. 7 days after the booster, GMCs escalated to around 10,781.6 EU/mL for group 1 and 10,746.9 EU/mL for group 2, nearly 39 times higher than pre-booster levels. A year after the booster, the GMC in group 1 was observed at 2133.1 EU/mL, 7.6 times above their pre-booster levels.

“We observed a decrease in the presence of vaccine-induced antibodies between day 78 and day 365 for group 1, and between day 78 and day 730 for group 2 but with a stabilization between day 365 and 730 at a GMC similar to that of the day 57 visit,” according to the investigators. “This finding was consistent with studies of the same vaccine regimen that observed a decline between day 78 and 6 months after the first dose (a timepoint not assessed in our trial), after which the circulating antibody concentration stabilized at a concentration similar to day 57 values.”

3 Key Takeaways

  1. Participants who received a booster dose of Ad26.ZEBOV either 1 year or 2 years after the initial vaccination exhibited a comparable and robust humoral immune response. This indicates that the timing for booster administration can be flexible, allowing for tailored vaccination schedules that could accommodate varying levels of Ebola virus exposure risk among populations.
  2. GMCs of Ebola virus glycoprotein-specific IgG binding antibodies saw an approximately 39-fold increase from pre-booster levels just 7 days after administrating the booster dose.
  3. The study also highlights the vaccine and booster's safety profile, they were well-tolerated among participants, with the most common adverse events being injection site pain or tenderness and headaches.

This open-label, single-center, randomized, phase 2 study was at a single hospital in Boende, Democratic Republic of the Congo. It involved adult healthcare providers and frontline workers, with individuals having a history of Ebola virus disease excluded. Participants received a 2-dose, different-component vaccine schedule, with injections 56 days apart. The first dose was Ad26.ZEBOV and the second MVA-BN-Filo, each administered as a 0.5 mL intramuscular shot in the deltoid muscle.

“We assessed serious adverse events occurring up to 6 months after the last dose and local and systemic solicited and unsolicited adverse events reported for 7 days after the booster vaccination,” according to investigators. “Antibody responses were analyzed per protocol, serious adverse events per FAS, and adverse events for all boosted FAS participants.”

319 participants in group 1 and 317 in group 2 received booster doses. Dropout rates were 8% in group 1 and 7% in group 2, mainly due to loss to follow-up or relocation. The most reported adverse events were injection site pain or tenderness (27% in group 1 and 28% in group 2) and headaches (29% in both groups), which were related to the vaccine. There was 1 serious adverse event reported in group 2, where a participant developed a fever of ≥40.0°C following the booster.

This study faced limitations, enrolling 700 participants within 3 years as part of a 4-year project made it hard to schedule a blood collection for group 2 a year after their booster shot. This made it difficult to compare long-term antibody persistence between the 2 groups post-booster. Assessing neutralizing anti-Ebola virus antibodies due to budget constraints for a large participant group. Studies in non-human primates informed the decision to focus on binding antibodies, which indicated a significant link between binding antibody levels and survival.

The study showed that the vaccine and booster dose were well tolerated, with Ebola virus glycoprotein binding antibodies lasting up to 2 years after the initial vaccine. The findings support considering the Ad26.ZEBOV booster for individuals at risk of Ebola, such as healthcare providers, up to two years after the primary vaccine.


1. Larvière Y, Matuvanga T, Osang’ir B, Milolo S, et. al. Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccine regimen plus Ad26.ZEBOV booster at 1 year versus 2 years in health-care and front-line workers in the Democratic Republic of the Congo: secondary and exploratory outcomes of an open-label, randomized, phase 2 trial. The Lancet. Published March 26, 2024. Accessed March 27, 2024. doi: https://doi.org/10.1016/S1473-3099(24)00058-6

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