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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9fcd68f95a2b493f8092a3429bbfd28d
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spelling	oai:doaj.org-article:9fcd68f95a2b493f8092a3429bbfd28d2021-12-02T10:48:30ZDurable natural killer cell responses after heterologous two-dose Ebola vaccination10.1038/s41541-021-00280-02059-0105https://doaj.org/article/9fcd68f95a2b493f8092a3429bbfd28d2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00280-0https://doaj.org/toc/2059-0105Abstract 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.Helen R. WagstaffeGiada SusanniniRodolphe ThiébautLaura RichertYves LévyViki BockstalJeroen N. StoopKerstin LuhnMacaya DouoguihEleanor M. RileyChristine LacabaratzMartin R. GoodierNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
title	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_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_sort	durable natural killer cell responses after heterologous two-dose ebola vaccination
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9fcd68f95a2b493f8092a3429bbfd28d
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Durable natural killer cell responses after heterologous two-dose Ebola vaccination

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