Trial reportThe Journal of clinical investigation2020
Ebola virus glycoprotein stimulates IL-18-dependent natural killer cell responses.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02313077 (A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability and Immunogenicity of Heterologous Prime-Boost Regimens Using MVA-BN®-Filo and Ad26.ZEBOV Administered in Different Sequences and Schedules in Healthy Adults), which is not on this map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1, First-in-Human Study to Evaluate the Safety, Tolerability and Immunogenicity of Heterologous Prime-Boost Regimens Using MVA-BN®-Filo and Ad26.ZEBOV Administered in Different Sequences and Schedules in Healthy Adults
Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose.NPJ vaccines · 2024Article
- Fully human monoclonal antibodies against Ebola virus possess complete protection in a hamster model.Emerging microbes & infections · 2024Article
- Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1.Scientific reports · 2023Article
- Characterization of an air-liquid interface primary human vaginal epithelium to study Ebola virus infection and testing of antivirals.Antiviral research · 2023Article
- Development of Modified Vaccinia Virus Ankara-Based Vaccines: Advantages and Applications.Vaccines · 2022Review
- Ebola virus protein VP40 stimulates IL-12- and IL-18-dependent activation of human natural killer cells.JCI insight · 2022Article
- NK Cell Subset Redistribution and Antibody Dependent Activation after Ebola Vaccination in Africans.Vaccines · 2022Article
- Activation of TLR4 by viral glycoproteins: A double-edged sword?Frontiers in microbiology · 2022Review
- Targeting natural killer cells to enhance vaccine responses.Trends in pharmacological sciences · 2021Review
- Durable natural killer cell responses after heterologous two-dose Ebola vaccination.NPJ vaccines · 2021Article
- Regulation of the human NK cell compartment by pathogens and vaccines.Clinical & translational immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUNDNK 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 analyzed 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 PBMCs 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, whereas 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 glycoprotein.TRIAL REGISTRATIONClinicalTrials.gov NCT02313077.FUNDINGUnited Kingdom Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (grant 115861) and Crucell Holland (now Janssen Vaccines and Prevention B.V.), European Union's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.