Immune Responses to Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccine in EBL2001 Phase 2 Trial

Overview

The Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine induced early serum inflammatory marker increases and durable EBOV-specific T-cell proliferation with cytotoxic CD8+ T-cell phenotypes. Integrated analyses revealed correlations between T-cell cytotoxicity and lower inflammatory IL-8 levels postvaccination, highlighting the vaccine's immunogenic potency.

Background

Ebola virus disease (EVD) remains a major global health threat with recurrent outbreaks in Africa. Vaccination is critical for outbreak control, with two vaccines authorized for emergency use: the rVSV-based Ervebo and the heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo regimen. The latter received European approval in 2020 after demonstrating safety and humoral immunogenicity in phase 2 trials. Understanding both innate and adaptive immune responses to this vaccine is essential to optimize its protective efficacy.

Data Highlights

Key Findings

• The vaccine induced a transient increase in serum inflammatory and activation markers, peaking one day after the Ad26.ZEBOV prime dose.
• EBOV-specific T-cell proliferation was robust and sustained through the MVA-BN-Filo boost and up to six months postvaccination.
• CD8+ T cells exhibited a cytotoxic phenotype, indicating functional cellular immunity elicited by the vaccine.
• Integrated analyses showed a positive correlation between EBOV-specific CD8+ T-cell proliferation and cytotoxic phenotype.
• An inverse correlation was observed between high CD8+ T-cell cytotoxicity and low IL-8 inflammatory marker levels at day 1 postvaccination.

Clinical Implications

These findings support the role of both innate inflammation and adaptive cellular immunity in the protective response induced by the Ad26.ZEBOV, MVA-BN-Filo vaccine. Monitoring T-cell proliferation and cytotoxic function alongside inflammatory markers may inform vaccine efficacy assessments and optimization. The durable cellular responses suggest potential for long-term protection against Ebola virus disease.

Conclusion

The Ad26.ZEBOV, MVA-BN-Filo vaccine elicits a coordinated immune response characterized by early inflammation and sustained EBOV-specific cytotoxic CD8+ T-cell activity. This integrated immune profile underpins its clinical efficacy and supports its use in Ebola outbreak control.

References

1. EBL2001 Phase 2 Trial Ancillary Study, 2024 -- Evaluation of Innate and Adaptive Immune Responses to the Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccine