Cross-reactive antibody and functional T-cell responses to Bundibugyo virus induced by Zaire ebolavirus vaccination and infection
- 1Vaccine Research Institute
Abstract
Background There is no licensed specific vaccine against the current Ebola Bundibugyo virus (BDBV) outbeak affecting the Democratic Republic of the Congo. However, clinical evaluations of a licensed Zaire ebolavirus (EBOV) vaccine have just launched. It remains unclear whether EBOV infection or vaccination generate cross-reactive immunity against BDBV. Methods We quantified CD4 and CD8 T-cell magnitude, polyfunctionality, and cytotoxicity after 8-day expansion with EBOV, BDBV, Sudan (SUDV), or Marburg (MARV) GP peptide pools, and measured GP-binding antibodies by multiplex assay, in recipients of Ad26.ZEBOV/MVA-BN-Filo (n=10), single-dose rVSVG-ZEBOV-GP (n=10), or two-dose rVSVG-ZEBOV-GP (n=8) (NCT02876328), and in EVD survivors sampled approximately 3 years after infection (n=10). Findings Fourteen days after completion of each licensed vaccine regimen, median BDBV-reactive CD4 responses were 9.8% [IQR:8.9-14.0] after single-dose rVSVG-ZEBOV-GP (D14) and 8.0% [5.5-9.9] after Ad26.ZEBOV/MVA-BN-Filo (D70). The highest BDBV-reactive CD8response was observed in survivors (24.7% [20.3-33.1]), together with a prominent cytotoxic CD8 response (14.4% [10.4-19.7]) ; corresponding vaccine-group medians ranged from 0.9% to 17.7% and from 0.6% to 6.7%, respectively. SUDV responses were also detected, whereas MARV recognition was limited. BDBV-binding antibodies were detected following both vaccine regimens, with the highest levels observed in survivors (491 [330-1261] net MFI). Among vaccinees, EBOV- and BDBV-reactive cellular and humoral responses were positively correlated after adjustment for multiple testing. Interpretation EBOV infection and vaccination elicited BDBV-cross-reactive T-cell responses and binding antibodies. These findings support further evaluation of existing EBOV vaccines in the context of BDBV outbreaks. Funding INSERM, Vaccine Research Institute (ANR-10-LABX-77-01), and Institut de Recherche pour le Developpement (IRD).
Related
- VSV-EBOV vaccination induces cross-reactive T-cell responses against Bundibugyo virus in humans
- Beyond viral species: the increasing mortality burden of the ongoing Bundibugyo ebolavirus outbreak in the Democratic Republic of the Congo
- Impact of Detection-Isolation-Leakage on the 2026 DRC Bundibugyo Ebolavirus Outbreak
- Evidence for cross-reactivity and protection against Bundibugyo virus disease after heterologous vaccination: a systematic review and meta-analysis
- Cross-Reactive Bundibugyo Antibody Responses after Receipt of Licensed Ebola Vaccines
BibTeX
@misc{wiedemann2026crossreactive,
title = {{Cross-reactive antibody and functional T-cell responses to Bundibugyo virus induced by Zaire ebolavirus vaccination and infection}},
author = {A. Wiedemann and A. Ayouba and E. Lhomme and E. Foucat and S. Kisrani and G. Thaurignac and S. Ben-Farhat and Postebogui Study group and PREVAC study team and M. Peeters and Y. Levy},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.03.26367168},
url = {https://www.medrxiv.org/content/10.64898/2026.11.03.26367168v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Cross-reactive antibody and functional T-cell responses to Bundibugyo virus induced by Zaire ebolavirus vaccination and infection
AU - A. Wiedemann
AU - A. Ayouba
AU - E. Lhomme
AU - E. Foucat
AU - S. Kisrani
AU - G. Thaurignac
AU - S. Ben-Farhat
AU - Postebogui Study group
AU - PREVAC study team
AU - M. Peeters
AU - Y. Levy
PY - 2026
DA - 2026/11/03
PB - medRxiv
DO - 10.64898/2026.11.03.26367168
UR - https://www.medrxiv.org/content/10.64898/2026.11.03.26367168v1
AB - Background There is no licensed specific vaccine against the current Ebola Bundibugyo virus (BDBV) outbeak affecting the Democratic Republic of the Congo. However, clinical evaluations of a licensed Zaire ebolavirus (EBOV) vaccine have just launched. It remains unclear whether EBOV infection or vaccination generate cross-reactive immunity against BDBV. Methods We quantified CD4 and CD8 T-cell magnitude, polyfunctionality, and cytotoxicity after 8-day expansion with EBOV, BDBV, Sudan (SUDV), or Marburg (MARV) GP peptide pools, and measured GP-binding antibodies by multiplex assay, in recipients of Ad26.ZEBOV/MVA-BN-Filo (n=10), single-dose rVSVG-ZEBOV-GP (n=10), or two-dose rVSVG-ZEBOV-GP (n=8) (NCT02876328), and in EVD survivors sampled approximately 3 years after infection (n=10). Findings Fourteen days after completion of each licensed vaccine regimen, median BDBV-reactive CD4 responses were 9.8% [IQR:8.9-14.0] after single-dose rVSVG-ZEBOV-GP (D14) and 8.0% [5.5-9.9] after Ad26.ZEBOV/MVA-BN-Filo (D70). The highest BDBV-reactive CD8response was observed in survivors (24.7% [20.3-33.1]), together with a prominent cytotoxic CD8 response (14.4% [10.4-19.7]) ; corresponding vaccine-group medians ranged from 0.9% to 17.7% and from 0.6% to 6.7%, respectively. SUDV responses were also detected, whereas MARV recognition was limited. BDBV-binding antibodies were detected following both vaccine regimens, with the highest levels observed in survivors (491 [330-1261] net MFI). Among vaccinees, EBOV- and BDBV-reactive cellular and humoral responses were positively correlated after adjustment for multiple testing. Interpretation EBOV infection and vaccination elicited BDBV-cross-reactive T-cell responses and binding antibodies. These findings support further evaluation of existing EBOV vaccines in the context of BDBV outbreaks. Funding INSERM, Vaccine Research Institute (ANR-10-LABX-77-01), and Institut de Recherche pour le Developpement (IRD).
ER -