npj Vaccines (Jan 2021)

Durable natural killer cell responses after heterologous two-dose Ebola vaccination

  • Helen R. Wagstaffe,
  • Giada Susannini,
  • Rodolphe Thiébaut,
  • Laura Richert,
  • Yves Lévy,
  • Viki Bockstal,
  • Jeroen N. Stoop,
  • Kerstin Luhn,
  • Macaya Douoguih,
  • Eleanor M. Riley,
  • Christine Lacabaratz,
  • Martin R. Goodier

DOI
https://doi.org/10.1038/s41541-021-00280-0
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 10

Abstract

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Abstract Natural killer (NK) cells are implicated among immune effectors after vaccination against viral pathogens, including Ebola virus. The two-dose heterologous Ebola virus vaccine regimen, adenovirus type 26.ZEBOV followed by modified vaccinia Ankara-BN-Filo (EBOVAC2 consortium, EU Innovative Medicines Initiative), induces NK cell activation and anti-Ebola glycoprotein (GP) antibody-dependent NK cell activation post-dose 1, which is further elevated post-dose 2. Here, in a multicentre, phase 2 clinical trial (EBL2001), we demonstrate durable ex vivo NK cell activation 180 days after dose 2, with responses enriched in CD56bright NK cells. In vitro antibody-dependent responses to immobilised Ebola GP increased after dose 1, and remained elevated compared to pre-vaccination levels in serum collected 180 days later. Peak NK cell responses were observed post-dose 2 and NK cell IFN-γ responses remained significantly elevated at 180 days post-dose 2. Individual variation in NK cell responses were influenced by both anti-Ebola GP antibody concentrations and intrinsic interindividual differences in NK cell functional capacity. In summary, this study demonstrates durable NK cell responses after Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccination and could inform the immunological evaluation of future iterations of the vaccine regimen and vaccination schedules.