Cross-reactive antibody and functional T-cell responses to Bundibugyo virus induced by Zaire ebolavirus vaccination and infection
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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 rVSVΔG-ZEBOV-GP (n=10), or two-dose rVSVΔG-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 rVSVΔG-ZEBOV-GP (D14) and 8.0% [5.5-9.9] after Ad26.ZEBOV/MVA-BN-Filo (D70). The highest BDBV-reactive CD8⁺ response 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.
