Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BackgrounNK cells are activated by innate cytokines and viral ligands to kill virus-infected cells; these functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined.MethodsThe novel 2-dose heterologous Adenovirus type 26.ZEBOV (Ad26.ZEBOV) and modified vaccinia Ankara-BN-Filo (MVA-BN-Filo) vaccine regimen is safe and provides specific immunity against Ebola glycoprotein, and is currently in phase 2 and 3 studies. Here, we analysed NK cell phenotype and function in response to Ad26.ZEBOV, MVA-BN-Filo vaccination regimen, and in response to in vitro Ebola glycoprotein stimulation of PBMC isolated before and after vaccination.ResultsWe show enhanced NK cell proliferation and activation after vaccination compared with baseline. Ebola glycoprotein-induced activation of NK cells was dependent on accessory cells and TLR-4-dependent innate cytokine secretion (predominantly from CD14+ monocytes) and enriched within less differentiated NK cell subsets. Optimal NK cell responses were dependent on IL-18 and IL-12, whilst IFN-γ secretion was restricted by high concentrations of IL-10.ConclusionThis study demonstrates the induction of NK cell effector functions early after Ad26.ZEBOV, MVA-BN-Filo vaccination and provides a mechanism for the activation and regulation of NK cells by Ebola GP.Trial Identifier: NCT02313077FundingU.K. Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (Grant 115861) and Crucell Holland (now Janssen Vaccines & Prevention B.V.), European Union's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA).

Original publication




Journal article


The Journal of clinical investigation


American Society for Clinical Investigation

Publication Date



Immunology, NK cells, Cytokines, Innate immunity, Vaccines