Cross-reactive antibody and functional T-cell responses to Bundibugyo virus induced by Zaire ebolavirus vaccination and infection

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).