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

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 vacciniaAnkara-BN-Filo (EBOVAC2 consortium, EU Innovative Medicines Initiative), inducesNK cell activation and anti-Ebola glycoprotein (GP) antibody-dependent NK cellactivation post-dose 1, which is further elevated post-dose 2. Here, in a multi-centre,phase 2 clinical trial (EBL2001), we demonstrate durable ex vivo NK cell activation180 days after dose 2, with responses enriched in CD56bright NK cells. In vitroantibody-dependent responses to immobilised Ebola GP increased after dose 1 andremained 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-responses remained significantly elevated 180 days post-dose 2. Individual variation in NK cell responses is influenced by both anti-Ebola GP antibody concentrationsand intrinsic inter-individual 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 immunological evaluation of future iterations of the vaccine regimen and vaccination schedules.