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 M...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-021-00280-0 |
| _version_ | 1797423369638903808 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Helen R. Wagstaffe |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T07:45:39Z |
| format | Article |
| id | doaj.art-9fcd68f95a2b493f8092a3429bbfd28d |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T07:45:39Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-9fcd68f95a2b493f8092a3429bbfd28d2023-12-03T03:28:43ZengNature Portfolionpj Vaccines2059-01052021-01-016111010.1038/s41541-021-00280-0Durable natural killer cell responses after heterologous two-dose Ebola vaccinationHelen R. Wagstaffe0Giada Susannini1Rodolphe Thiébaut2Laura Richert3Yves Lévy4Viki Bockstal5Jeroen N. Stoop6Kerstin Luhn7Macaya Douoguih8Eleanor M. Riley9Christine Lacabaratz10Martin R. Goodier11Department of Infection Biology, London School of Hygiene and Tropical MedicineDepartment of Infection Biology, London School of Hygiene and Tropical MedicineUniv. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219; CHU Bordeaux; CIC 1401, EUCLID/F-CRIN Clinical Trials PlatformUniv. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219; CHU Bordeaux; CIC 1401, EUCLID/F-CRIN Clinical Trials PlatformInserm U955, Vaccine Research Institute, Université Paris-Est Créteil, Hôpital Henri MondorJanssen Vaccines and PreventionJanssen Vaccines and PreventionJanssen Vaccines and PreventionJanssen Vaccines and PreventionDepartment of Infection Biology, London School of Hygiene and Tropical MedicineInserm U955, Vaccine Research Institute, Université Paris-Est Créteil, Hôpital Henri MondorDepartment of Infection Biology, London School of Hygiene and Tropical MedicineAbstract 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.https://doi.org/10.1038/s41541-021-00280-0 |
| spellingShingle | 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 Durable natural killer cell responses after heterologous two-dose Ebola vaccination npj Vaccines |
| title | Durable natural killer cell responses after heterologous two-dose Ebola vaccination |
| title_full | Durable natural killer cell responses after heterologous two-dose Ebola vaccination |
| title_fullStr | Durable natural killer cell responses after heterologous two-dose Ebola vaccination |
| title_full_unstemmed | Durable natural killer cell responses after heterologous two-dose Ebola vaccination |
| title_short | Durable natural killer cell responses after heterologous two-dose Ebola vaccination |
| title_sort | durable natural killer cell responses after heterologous two dose ebola vaccination |
| url | https://doi.org/10.1038/s41541-021-00280-0 |
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