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

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.

CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination

“…In the ChAdOx1 S-D cohort, we observed more CD107a expression in the CMV-seronegative participants following vaccination; however, in the ChAdOx1-MVA and ChAd3-MVA cohorts, CMV-seropositive individuals expressed more CD107a after vaccination. Previous studies have found either no effect of CMV infection on NK cell CD107a expression ( 18 , 52 ) or reduced expression with CMV seropositivity ( 19 ). Increased expression of CD107a in our cohorts may be due to a proportional increase in CD57 + NK cells in CMV + participants, which are less reactive to activation by cytokines and cytokine secretion but are still able to degranulate following stimulation ( 48 ).…”

“…Other research demonstrates that humoral responses are also reduced in CMV seropositive older adults vaccinated against influenza (10,11,15). Furthermore, NK cell functionality and cytotoxicity is reduced in some vaccinated individuals with CMV (16)(17)(18)(19). In contrast, other research has shown increased humoral responses to influenza vaccination in adults with CMV (20)(21)(22)(23), or no discernible correlation between CMV serostatus and vaccine response (8,9,24,25).…”

NK Cell Subset Redistribution and Antibody Dependent Activation after Ebola Vaccination in Africans

“…These studies in European trials also demonstrate that this vaccine induces a redistribution of NK cell subsets towards less differentiated CD56 bright and CD57 − NK cells accompanied by increased frequency of CD25 + NK cells, suggesting potential for increased responsiveness to CD4 + T cell derived IL-2 (CD25 expression) and proliferation 21 days after the second vaccine dose [14]. Further, we demonstrated persistent redistribution of NK cell subsets up to 180 days post-dose 2, also involving an enrichment of CD56 bright NK cells and enhanced CD25 expression [15].…”

A Case-Control Study on the Changes in Natural Killer Cell Activity following Administration of Polyvalent Mechanical Bacterial Lysate in Korean Adults with Recurrent Respiratory Tract Infection

“…Hence, vaccines may mimic the infection process, triggering an immune response, including NK cell activation. NK cell response in humans has been shown to increase after vaccination with influenza and Ebola virus vaccines [ 30 , 31 ]. PMBL is an oral immunostimulant consisting of standardized bacterial lysates obtained by the lysis of different strains of Gram-positive and Gram-negative pathogens that cause respiratory tract infections [ 12 ].…”