Cross-Reactive T-Cell Responses Against Bundibugyo Virus Following VSV-EBOV Vaccination in Humans
Presentation by Dr. Leonie Mayer - Scientific Lunchsymposium at the 55th Annual Meeting of the German Society for Immunology (DGfI) in Munich
The ongoing outbreak of the Bundibugyo virus (BDBV) in the Democratic Republic of Congo (DRC) highlights the urgent need for effective countermeasures against this virus. „With more than 6,000 cases, the outbreak has expanded to 61 different health districts within the Democratic Republic of Congo. The epicenter of the outbreak continues to be in Ituri, which is a very resource-limited area that is also torn by conflicts, so it's really difficult to contain this outbreak at the moment“, explained Dr. Leonie Mayer from the University Medical Center Hamburg-Eppendorf (UKE).
BDBV is closely related to Ebola virus (EBOV) and Sudan virus (SUDV). Because there is currently no licensed vaccine or specific treatment for BDBV, the question arises: can the established EBOV vaccine (rVSV-ZEBOV) provide cross-protection?
Background: High Sequence Conservation and Open Questions
The rVSV-ZEBOV vaccine uses a recombinant vesicular stomatitis viral vector expressing the EBOV glycoprotein (GP). It demonstrated 100% efficacy against EBOV during clinical trials and 84% effectiveness during the 2018-2020 EBOV in the DRC.
- Conserved Regions: The glycoprotein – the main surface antigen – shares 66% amino acid sequence identity between EBOV and BDBV, with conserved regions spanning key functional domains such as the receptor-binding domain.
- Humoral Cross-Reactivity: Non-human primate models and clinical trials show that VSV-EBOV vaccination induces BDBV-reactive neutralizing antibodies. However, these antibody titers are generally lower than those against EBOV and do not consistently correlate with survival in non-human primate models.
„Mire et al. could show that three out of four animals that had been vaccinated with a combination of VSV-EBOV and VSV-SUDV survived a BDBV challenge, and here higher BDBV-cross-reactive antibody titers were associated with survival“, outlined Dr. Mayer the results of one non-human primate study. [1]
Because T cells play a pivotal role in preventing severe disease and target highly conserved regions less prone to mutational drift, Dr. Mayer and co-workers investigated whether VSV-EBOV vaccination also elicits cross-reactive T-cell responses against BDBV in humans. [2]
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Study Design & Methodology
Samples from a previous Phase I clinical trial assessing the VSV-EBOV vaccine were evaluated, comparing 20 VSV-EBOV-vaccinated individuals against 7 healthy controls.
- Ex Vivo Restimulation: Peripheral blood mononuclear cells (PBMCs) were restimulated using synthetic peptide pools covering the glycoproteins of EBOV, SUDV, and BDBV.
- Assay: Antigen-specific T cells were quantified using an IFN-γ ELISpot assay.
- Mapping Conserved Regions: Based on sequence alignments, five peptide pools were designed to specifically cover highly conserved regions across the viral glycoproteins.
Key Findings
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Robust Cross-Reactive T-Cell Immunity:
- 16 out of 20 vaccinated individuals exhibited T-cell reactivity against EBOV.
- 13 out of 20 individuals displayed cross-reactive T-cell responses against the Bundibugyo virus glycoprotein.
- Overall BDBV-specific T-cell responses were significantly elevated compared to healthy controls and positively correlated with EBOV-specific responses.
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Recognition of Conserved Epitopes:
- All five custom peptide pools covering conserved glycoprotein regions were recognized by T cells of vaccinated participants (at least 4 participants responding per pool).
Conclusion & Clinical Significance
„With these results, we could show for the first time that VSV-EBOV vaccination does induce cross-reactive T-cell responses against Bundibugyo virus in humans, and that these T-cells can also recognize conserved regions within the glycoprotein“, Dr. Mayer highlighted their findings. While it remains unknown if VSV-EBOV can provide clinical efficacy against BDBV, the combination of cross-reactive cellular and humoral immune data supports WHO recommendations to evaluate the VSV-EBOV vaccine under research protocols during the current BDBV outbreak.
Dr. Mayer expressed her thanks to the teams at the UKE in Hamburg and the LMU in Munich for engineering this project and designing the peptide pools, as well as the European Vaccines Hub for pandemic preparedness, the German Center for Infection Research (DZIF) and the Collaborative research Center 1648 “Emerging Viruses” for funding.
Literature
- Mire, Chad E et al. “Vesicular stomatitis virus-based vaccines protect nonhuman primates against Bundibugyo ebolavirus.” PLoS neglected tropical diseases vol. 7,12 e2600. 19 Dec. 2013, doi:10.1371/journal.pntd.0002600
- Mayer, Leonie et al. “Cross-reactive T-cell responses against BDBV in humans after rVSVΔG-ZEBOV-GP vaccination.” The Lancet. Infectious diseases, S1473-3099(26)00529-3. 13 Oct. 2026, doi:10.1016/S1473-3099(26)00529-3